DNA Structure amp Function (Outline)1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rulebull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
By definition the genetic material of must
bull be replicated DNA Replication
bull direct the cell functions by providing information for production of proteins
Flow of the genetic information(Gene Expression)
Current Connections to
DNA structure and replication
Why are we mortal with a limited life span
DNA as the Genetic MaterialTime-line
1850rsquos Mendel 1870-1890 Microsocopy Mitosis and Meiosis1902 Chromosome basis of inheritance
(Thomas H Morgan)20th century Work with bacteria and viruses
1928 Fredrick Griffith ExperimentsConcept of transformation (using Bacteria that cause pneumonia in mammals)
1944 Avery McCarty and MacLeodThe transforming material is DNAldquoDNA is the genetic materialrdquo
1952 Hershey and ChaseDNA is the genetic material in viruses that infect bacteria
Griffith- Phenomenon of Transformation a change in genotype (genetic makeup) by a foreign substance that
changes the phenotype (observed properties) of the cell
History of DNAAvery MacLeod and McCarty 1944
- DNA is the transforming material
(Can convert Type R bacteria into S)
bull A phage is a virus that infects bacteria and is made of DNA and protein
bull Alfred Hershey and Martha Chase- the genetic material of the phage T2 is DNA
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
DNA Structure
Prior to the 1950s DNA is a polymer of nucleotides consisting ofbull a nitrogenous base bull a sugarbull a phosphate group
Polarity and anti-parallel nature of the two DNA strands (5rsquo and 3rsquo ends)
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
By definition the genetic material of must
bull be replicated DNA Replication
bull direct the cell functions by providing information for production of proteins
Flow of the genetic information(Gene Expression)
Current Connections to
DNA structure and replication
Why are we mortal with a limited life span
DNA as the Genetic MaterialTime-line
1850rsquos Mendel 1870-1890 Microsocopy Mitosis and Meiosis1902 Chromosome basis of inheritance
(Thomas H Morgan)20th century Work with bacteria and viruses
1928 Fredrick Griffith ExperimentsConcept of transformation (using Bacteria that cause pneumonia in mammals)
1944 Avery McCarty and MacLeodThe transforming material is DNAldquoDNA is the genetic materialrdquo
1952 Hershey and ChaseDNA is the genetic material in viruses that infect bacteria
Griffith- Phenomenon of Transformation a change in genotype (genetic makeup) by a foreign substance that
changes the phenotype (observed properties) of the cell
History of DNAAvery MacLeod and McCarty 1944
- DNA is the transforming material
(Can convert Type R bacteria into S)
bull A phage is a virus that infects bacteria and is made of DNA and protein
bull Alfred Hershey and Martha Chase- the genetic material of the phage T2 is DNA
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
DNA Structure
Prior to the 1950s DNA is a polymer of nucleotides consisting ofbull a nitrogenous base bull a sugarbull a phosphate group
Polarity and anti-parallel nature of the two DNA strands (5rsquo and 3rsquo ends)
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Current Connections to
DNA structure and replication
Why are we mortal with a limited life span
DNA as the Genetic MaterialTime-line
1850rsquos Mendel 1870-1890 Microsocopy Mitosis and Meiosis1902 Chromosome basis of inheritance
(Thomas H Morgan)20th century Work with bacteria and viruses
1928 Fredrick Griffith ExperimentsConcept of transformation (using Bacteria that cause pneumonia in mammals)
1944 Avery McCarty and MacLeodThe transforming material is DNAldquoDNA is the genetic materialrdquo
1952 Hershey and ChaseDNA is the genetic material in viruses that infect bacteria
Griffith- Phenomenon of Transformation a change in genotype (genetic makeup) by a foreign substance that
changes the phenotype (observed properties) of the cell
History of DNAAvery MacLeod and McCarty 1944
- DNA is the transforming material
(Can convert Type R bacteria into S)
bull A phage is a virus that infects bacteria and is made of DNA and protein
bull Alfred Hershey and Martha Chase- the genetic material of the phage T2 is DNA
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
DNA Structure
Prior to the 1950s DNA is a polymer of nucleotides consisting ofbull a nitrogenous base bull a sugarbull a phosphate group
Polarity and anti-parallel nature of the two DNA strands (5rsquo and 3rsquo ends)
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
DNA as the Genetic MaterialTime-line
1850rsquos Mendel 1870-1890 Microsocopy Mitosis and Meiosis1902 Chromosome basis of inheritance
(Thomas H Morgan)20th century Work with bacteria and viruses
1928 Fredrick Griffith ExperimentsConcept of transformation (using Bacteria that cause pneumonia in mammals)
1944 Avery McCarty and MacLeodThe transforming material is DNAldquoDNA is the genetic materialrdquo
1952 Hershey and ChaseDNA is the genetic material in viruses that infect bacteria
Griffith- Phenomenon of Transformation a change in genotype (genetic makeup) by a foreign substance that
changes the phenotype (observed properties) of the cell
History of DNAAvery MacLeod and McCarty 1944
- DNA is the transforming material
(Can convert Type R bacteria into S)
bull A phage is a virus that infects bacteria and is made of DNA and protein
bull Alfred Hershey and Martha Chase- the genetic material of the phage T2 is DNA
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
DNA Structure
Prior to the 1950s DNA is a polymer of nucleotides consisting ofbull a nitrogenous base bull a sugarbull a phosphate group
Polarity and anti-parallel nature of the two DNA strands (5rsquo and 3rsquo ends)
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
1928 Fredrick Griffith ExperimentsConcept of transformation (using Bacteria that cause pneumonia in mammals)
1944 Avery McCarty and MacLeodThe transforming material is DNAldquoDNA is the genetic materialrdquo
1952 Hershey and ChaseDNA is the genetic material in viruses that infect bacteria
Griffith- Phenomenon of Transformation a change in genotype (genetic makeup) by a foreign substance that
changes the phenotype (observed properties) of the cell
History of DNAAvery MacLeod and McCarty 1944
- DNA is the transforming material
(Can convert Type R bacteria into S)
bull A phage is a virus that infects bacteria and is made of DNA and protein
bull Alfred Hershey and Martha Chase- the genetic material of the phage T2 is DNA
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
DNA Structure
Prior to the 1950s DNA is a polymer of nucleotides consisting ofbull a nitrogenous base bull a sugarbull a phosphate group
Polarity and anti-parallel nature of the two DNA strands (5rsquo and 3rsquo ends)
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Griffith- Phenomenon of Transformation a change in genotype (genetic makeup) by a foreign substance that
changes the phenotype (observed properties) of the cell
History of DNAAvery MacLeod and McCarty 1944
- DNA is the transforming material
(Can convert Type R bacteria into S)
bull A phage is a virus that infects bacteria and is made of DNA and protein
bull Alfred Hershey and Martha Chase- the genetic material of the phage T2 is DNA
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
DNA Structure
Prior to the 1950s DNA is a polymer of nucleotides consisting ofbull a nitrogenous base bull a sugarbull a phosphate group
Polarity and anti-parallel nature of the two DNA strands (5rsquo and 3rsquo ends)
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
History of DNAAvery MacLeod and McCarty 1944
- DNA is the transforming material
(Can convert Type R bacteria into S)
bull A phage is a virus that infects bacteria and is made of DNA and protein
bull Alfred Hershey and Martha Chase- the genetic material of the phage T2 is DNA
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
DNA Structure
Prior to the 1950s DNA is a polymer of nucleotides consisting ofbull a nitrogenous base bull a sugarbull a phosphate group
Polarity and anti-parallel nature of the two DNA strands (5rsquo and 3rsquo ends)
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
bull A phage is a virus that infects bacteria and is made of DNA and protein
bull Alfred Hershey and Martha Chase- the genetic material of the phage T2 is DNA
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
DNA Structure
Prior to the 1950s DNA is a polymer of nucleotides consisting ofbull a nitrogenous base bull a sugarbull a phosphate group
Polarity and anti-parallel nature of the two DNA strands (5rsquo and 3rsquo ends)
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
DNA Structure
Prior to the 1950s DNA is a polymer of nucleotides consisting ofbull a nitrogenous base bull a sugarbull a phosphate group
Polarity and anti-parallel nature of the two DNA strands (5rsquo and 3rsquo ends)
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Polarity and anti-parallel nature of the two DNA strands (5rsquo and 3rsquo ends)
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Biochemical analysis of DNA Base-pairing rule
1947 Erwin Chargaff analysis of DNA from different species A = T amp C = G
Human DNA A = 309T = 294C = 199G = 198
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Base-pairing in DNA
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Maurice Wilkins and Rosalind Franklin- X-ray crystallography Polynucleotide Helix
Franklinrsquos X-ray diffractionPhotograph of DNA
(a) Rosalind Franklin (b)
Structural Model of DNA
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Watson and Crick deduced that DNA was a double-stranded helix Through observations of the X-ray crystallographic images of DNA
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Watson and Crick - Specificity of pairing is dictated by the structure of
the bases
Example
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Three models for DNA replicationConservative modelSemi-conservative modelDispersive model
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Bacteriacultured in mediumcontaining15N
DNA samplecentrifugedafter 20 min(after firstreplication)
DNA samplecentrifugedafter 40 min(after secondreplication)
Bacteriatransferred tomediumcontaining14N
Lessdense
Moredense
Meselson-Stahl experiment
httphigheredmcgraw-hillcomsites0072437316student_view0chapter14animationshtml
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
The Basic concept of DNA replication
Each strand of DNA act as a template for synthesis of new complementary strands
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Molecular Mechanism of DNA Replication
Collective action of several macro-molecules bull DNAbull Proteins (enzymes amp others)bull RNAbull Ribo-protein (for linear chromosomes)
Direction of replication of new strands 5rsquo-----3rsquo
How nucleotides are added in DNA replicationhttphigheredmcgraw-
hillcomsites0072437316student_view0chapter14animationshtmlCampbell Bio Flix DNA Replication
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
The new strand always starts with the 5rsquo end the template starts with the 3rsquo end
DNA polymerase adds deoxyribonucleotides in a 5rsquo to 3rsquo direction it adds nucleotides to the 3prime end of a growing strand
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Primase an RNA polymerase uses the DNA template strand to polymerize a short complementary RNA chain (RNA primer)
Two different DNA polymerases both- cannot initiate the synthesis of a polynucleotide- can only add nucleotides to an existing 3prime end
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Summary of DNA Replicationbull Semi-conservativebull Initiation Origin of replicationbull Primase and RNA primerbull Template strand vs new strandbull 5rsquo to 3rsquo directionbull DNA polymerase (III and I)bull Base-pairing rulesbull dNTPs deoxy-ATP deoxy-GTP deoxy-CTP deoxy-
TTPbull Leading and lagging strandsbull Okazaki fragmentsbull DNA ligasebull Bidirectionalbull Fidelity of DNA replication is maintained by activity of
DNA polymerase and other proof reading systems
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Origin of Replication
TP 7-14
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Other proteins participate in DNA replication including Helicase topoisomerase single-strand binding protein
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Replication of long DNA molecules begins at multiple origins of replication simultaneously and is bidirectional
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
DNA Structure amp Function1 Historical perspective (DNA as the genetic material)
bull Genetic transformation and DNAbull DNA is the genetic material in bacterial viruses (phage) bull The base-pairing rule bull DNA structure
2 Basis for polarity of SS DNA and anti-parallel complementary strands of DNA
3 DNA replication models4 Mechanism of DNA replication steps and molecular
machinery5 Replication and the end of linear chromosomes-
Molecular basis for aging6 Fidelity of DNA replication
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Lagging strand
5prime
3prime
Last fragment
RNA primer
Previous fragment
Primer removed butcannot be replacedwith DNA becauseno 3prime end available
for DNA polymerase
5prime
3prime
Removal of primers andreplacement with DNAwhere a 3prime end is available
Second roundof replication
5prime3prime5prime
3primeFurther roundsof replication
New leading strandNew leading strand
Shorter and shorterdaughter molecules
Replicating the Ends of linear DNA Molecules
Mechanism of DNA replication causes telomeres to get shorter with each round of replication
httpwwwlearnerorgcoursesbiologyunitscancerimageshtml
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Current Connections to
DNA structure and replication
Q Why are we mortal with a limited life span
A Our cells have a limited life span ( of cell divisions)
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Telomerase- an enzyme (riboprotein) that extends the 3rsquo end of the DNA strand by adding a repeated sequence of 6-nucleotides typically TTAGGG (100-1000 times)
httpswwwyoutubecomwatchv=AJNoTmWsE0s
httpswwwyoutubecomwatchv=vtXrehpCPEE
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Ends of linear chromosomes have special DNA sequences and are known as telomeres
added by an enzyme known as telomerase after DNA replication is completed
1
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Figure 23
Life span of dividing cellsbull Telomerase is active in sperm eggs stem cells (bone
marrow) and cancer cells but not in somatic tissuesbull Most cells lose 50-200 endmost bases after each cell
divisionbull After about 50 divisions shortened telomeres signal the
cell to stop dividing
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Fidelity of DNA replication amp maintaining DNA integrity
Maintained by
1 Proof-reading function of DNA polymerase2 DNA repair systemshttpwwwhhmiorgbiointeractivemediamismatch_repair-lgmov
DNA damage and repair in general httpwwwyoutubecomwatchv=y16w-CGAa0Yampfeature=relatedhttpwwwyoutubecomwatchv=nPS2jBq1k48
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected
Genetic Integrity and Diversity
bull Need for maintaining genetic integrity is balanced by having enough genetic variability for natural selection to act on
bull Few errors of DNA replication are not corrected