Unit 1-DNA-stucture & Function-C08 Roscoe 1e PPT

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Chapter 8

DNA Structure and Function

Prepared by

Wendi Roscoe

Fanshawe College

1Copyright © 2016 by Nelson Education Ltd.Copyright © 2016 by Nelson Education Ltd.

The Central Dogma

DNA RNA Protein

(nucleus) (nucleus) cytoplasm (ribosomes)

transcription translation

2Copyright © 2016 by Nelson Education Ltd.

8.1 DNA Structure

Nucleic acids are very long polymers that are made up of nucleotides.• Each nucleotide has three parts:

1. a five-carbon sugar (ribose or deoxyribose)

2. a phosphate group3. an organic nitrogen-containing base

What are the five nucleotides?


8.1 DNA Structure

• What do DNA and RNA stand for?

• What are the three differences between DNA and RNA?

1. DNA has thymine; RNA has uracil.2. DNA is double stranded; RNA is single

stranded.3. DNA has deoxyribose; RNA has ribose.


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8.1 DNA Structure

• The structure of DNA is a double helix.

• Only two base pairs are possible.• Adenosine (A) pairs with thymine (T).

• Cytosine (C) pairs with guanine (G).• The bond holding together a base pair is a

hydrogen bond.• The sugar-phosphate backbone consists of

phosphodiester bonds.


8.1 DNA Structure

Copyright © 2016 by Nelson Education Ltd. 6

8.1 DNA Structure

• The structure of DNA helps it to function.

• The hydrogen bonds of the base pairs can be easily broken to unzip the DNA so that information can be copied.• Each strand of DNA is a mirror image, so the

DNA contains two copies of the information.

• Having two copies means that the information can be accurately copied and passed to the next generation.


8.1 DNA Structure

• Nucleotides differ in regard to their bases.

• Large bases are called purines and have a double-ringstructure: Adenine and Guanine

• Small bases are called pyrimidines and have a single-ring structure: Cytosine and Thymine

• Edwin Chargaff noted that DNA molecules always have equal amounts of purines and pyrimidines.

• Chargaff’s rule suggests that DNA has a regular structure.• The amount of A always equals the amount of T.• The amount of C always equals the amount of G.


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8.1 DNA Structure

• Purines – adenine and guanine (double-ring structures)

• Pyrimidines – cytosine and thymine (single-ring structures)


8.1 DNA Structure

• The carbons on ribose and deoxyribose are numbered 1 to 5.


8.1 DNA Structure


8.1 DNA Structure

• Rosalind Franklin’s work in 1953 using X-ray defraction revealed that DNA had a regular structure that was shaped like a corkscrew, or helix.

• Francis Crick and James Watson elaborated on the discoveries of Franklin and Chargaff and deduced that the structure of DNA was a double helix.• Two strands of DNA bind together by their bases.• This happens because a purine of one strand binds

to a pyrimidine on the other strand.


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8.1 DNA Structure


8.1 DNA Structure

• ATP is a nucleoside triphosphate that is produced in all cells and is the primary source of energy for all cell functions.

• GTP can also be used as energy in cells.


8.1 DNA Structure – Nucleosides

• Our diet is the source of nucleosides in our cells that can be made into nucleotides for DNA replication, or for the transcription of RNA molecules.

• All plant and animal cells contain DNA and RNA.

• We have enzymes in our digestive tract that break down nucleic acids into individual nucleosides.


8.1 DNA Structure – Telomeres

• A telomere is a region of repetitive DNA at the end of every chromosome.

• Telomeres protect the end of the chromosome from deterioration.

• The telomere regions shorten during DNA replication because there is a gap left after the removal of the first 5’ end primer.

• Telomeres get shorter after every cell division.

• This is what causes our cells to have a specific lifespan, and this is why we age.


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8.1 DNA Structure


8.1 DNA Structure – Telomeres

• Prokaryotes do not have telomeres because their DNA is circular.

• An enzyme called telomerase is found in stem cells and germ cells (give rise to gametes), which replaces the telomere sequences.

• Cancer cells also produce telomerase, which is why cancer cells are immortalized (never die).

• This is also why a “telomerase drug” can’t be used to prevent aging.


DNA Trivia

• The average length of a single chromosome is 2 inches.

• We have 46 chromosomes in each cell.

• The total length of DNA per cell is about 2.3 metres.• All DNA in every cell of our body (about 50

trillion cells) would stretch to about 300 000 000 metres – it would reach to the moon.


8.2 DNA Replication

• The two strands of DNA that form the double helix DNA molecule are complementary to each other.

• Each chain is essentially a mirror image of the other.

• The hydrogen bonds that hold the base pairs together are weak bonds and, therefore, easy to separate.

• What is the complementary strand of this DNA sequence: 5’ GGTACCAGT 3’?


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8.2 DNA Replication


8.2 DNA Replication


8.2 DNA Replication

1. Replication begins at a point of origin; in eukaryotes there are many points of origin.

2. An enzyme called helicase unwinds the DNA.

3. The section where the DNA is unwound is called the replication fork.

4. Single-strand binding proteins stabilize the separated strands of DNA.

5. DNA polymerase moves along each strand of unwound DNA and adds the correct complementary nucleotides.


8.2 DNA Replication

5. DNA polymerase can only add new nucleotides to an existing strand of DNA.

6. Therefore, primase adds a small fragment of RNA (an RNA primer) to the initially separated DNA.

7. The RNA primer is complementary to the DNA, and this is later replaced with DNA.


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8.2 DNA Replication

8. Since the two DNA strands are antiparallel, one strand is oriented as 5’ to 3’, and the other strand is oriented 3’ to 5’.

9. Polymerase can only add new nucleotides to the 3’ end of the new DNA strand; this is called the leading strand.

10. The opposite strand is called the lagging strand.


8.2 DNA Replication

11. The lagging strand must be replicated in discontinuous segments called Okazaki fragments.

12. Each segment of the lagging strand must begin with an RNA primer, then polymerase can add nucleotides in the 5’ to 3’ direction. (This is the direction of the new strand being formed.)

13. Then each RNA primer is removed and replaced with DNA.

14. DNA ligase is the enzyme that covalently links the new segments of DNA after the RNA primer is removed – forms phosphodiester bonds.


8.2 DNA Replication


8.2 DNA Replication


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8.3 DNA Mutations

• Because so much DNA is being replicated in the many cells of the body, there is potential for errorsto occur,

• We have about 130 genes that code for DNA repair enzymes

• Repair enzymes, as well as polymerase itself, compare the new DNA strand with the original DNA strand and fix any incorrect nucleotides.• This is called proofreading.

• Proofreading is still not perfect and mistakes can occur – DNA mutations.

• What happens if there are mutations?


8.3 DNA Mutations

• How do our cells deal with mutations?• Proofreading• Repair enzymes

• What if mutations still occur?• Apoptosis (programed cell death)• Immune cells that kill cancer cells

• What if mutations still occur?• Disease


8.3 DNA Mutations

• There are two general ways to alter the genetic message encoded in DNA.

• Point mutations

• These result from errors in replication.• They can involve substitutions, additions, or

deletions of nucleotides.

• Recombination mutations• These cause change in the position of all or part

of a gene.


8.3 DNA Mutations

• Approximately one in every 100 000 to 1 million base pairs will be a mismatch (substitution) during replication.

• Generally, a mismatch causes polymerase to pause, and then the incorrect base pair enters the exonuclease section of the polymerase enzyme; this is proofreading.

• Then the error can be removed, and the correct nucleotides replace the mistake.


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8.3 DNA Mutations• As well as polymerase, repair enzymes can also

correct DNA mutations.

• What are the consequences of DNA mutations• in a population of organisms?• in that specific organism?

• What do you call a substance that mutates DNA?

• Mutagen

• What do you call a substance that mutates DNA and also causes cancer? • Carcinogen


8.3 DNA Mutations

• Mutations can alter the genetic message and affect protein synthesis.• Most mutations occur randomly in a cell’s DNA, so

most mutations are detrimental.

• In what cell types can DNA mutations occur?• Mutations in germ cells

• These mutations will be passed to future generations.

• They are important for evolutionary change.• Mutations in somatic cells

• These are not passed to future generations but are passed to all other somatic cells derived from them.


8.3 DNA Mutations


8.3 DNA Mutations

• There are different types of DNA mutations.1. Substitution (mismatch) changes the identity of a

base or bases.2. Insertion adds a base or bases.3. Deletion removes a base of bases.

• What would be the consequence of a deletion or addition?

• A frame-shift mutation results.• These are extremely detrimental because the final

protein intended by the message may be altered dramatically, or it may not be made at all.


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8.3 DNA Mutations

• THE CAT SAW THE DOG

• Substitution• THE BAT SAW THE DOG

• Insertion• THE CRA TSA WTH EDO G

• Deletion• THE ATS AWT HED OG


8.3 DNA Mutations – Transposition

• Transposable elements (TEs) are sequences of DNA that can move or transpose themselves within a cell.

• The mechanism of transposition can be either "copy and paste" or "cut and paste."

• All living organisms contain transposable elements (also called transposons, or jumping genes).

• TEs play a significant role in phenotypic variation and evolution, but they can be detrimental to an organism.


8.3 DNA Mutations – Transposition

• If a mutagen causes the sugar-phosphate backbone to break, the cell will try to repair this by adding the DNA fragment to another piece of DNA.

• This can cause segments of DNA to be moved to entirely different chromosomes.

• If this occurred in germ cells, how would this affect crossing over during meiosis?


8.3 DNA Mutations


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8.3 DNA Mutations


8.3 DNA Mutations – Introns and Exons

• Exons are the sequences in a gene that code for the mRNA that will code for the protein.

• Introns are removed and do not become part of the RNA sequence.

• Mutations in introns usually have no affect on the protein – silent mutations.

• Also, some mutations occur in a base that does not affect the protein sequence. (*This will be discussed later in more detail.)


8.3 DNA Mutations

• Natural killer cells can kill cancer cells.


8.3 DNA Mutations – Genetic Diseases

• Cystic fibrosis – one mismatch base in the gene that codes for chloride channels

• Huntington’s disease – insertion of multiple CAG repeats in a gene on chromosome 4

• Sickle cell anemia – one mismatch in the hemoglobin gene

• Cancer – usually two or more mutations in genes that code for repair enzymes, or genes that affect the cell cycle. What are these called?

• Oncogenes and tumour-suppressor genes


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8.3 DNA Mutations – Genetic Diseases

• Phenylketonuria (PKU) – point mutation in liver enzyme gene, which causes brain damage. Babies are tested at birth for presence of enzyme that breaks down phenylalanine into tyrosine (amino acids).

• Nonpolyposis colorectal cancer – autosomal dominant, repeated CA mutation in DNA repair enzyme gene, a non-functional repair protein


How do we acquire DNA mutations?

1. Mistakes during DNA replication

2. Transposition

3. Inherited mutations (approximately 10% of diseases are from inherited mutations)

4. Mutagens and carcinogens (most common cause)

5. Viruses


8.3 DNA Mutations – Mutagens

• Radiation• UV light. This is the most common cause of skin

cancers.• X-rays. Gamma radiation used for taking x-rays can

cause multiple types of cancers.

• Chemicals• Pesticides and herbicides• Industrial chemicals• Pollution, including cigarette smoke• Food additives and preservatives• Drugs


8.3 DNA Mutations – Mutagens

• Viruses• Human papilloma virus (HPV) – genital warts

that can cause cervical cancer• Human immunodeficiency virus (HIV) – AIDS,

which can cause Kaposi sarcoma, and overgrowth of blood vessels.

• Hepatitis B or C – liver infection that can cause liver cancer.

• Epstein Barr Virus (EBV) – mononucleosis, which can cause lymphoma (rare)


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Summary

• Central dogma: DNA – RNA – Protein

• DNA is a double helix with two strands that are antiparallel – purines bind with pyrimidines.

• Telomeres are end repeat sequences of DNA that shorten each time DNA replicates; telomerase prevents shortening in specific cell types.

• DNA replicates by semi-conservative replication.

• Enzymes involved in replication include helicase, primase, single-strand binding protein, polymerase, and ligase.


Summary• The leading strand replicates continuously, and the

lagging strand replicates using Okazaki fragments.

• Polymerase adds nucleotides to the 3’ end of a pre-existing nucleotide (5’ to 3’ direction on the new strand).

• Point mutations include substitutions, insertions, or deletions.

• Insertions and deletions cause frameshifts.

• Transposition mutations involve large sequences of DNA.

• Most DNA mutations are detrimental.


Summary

• Polymerase has proofreading ability and can fix many mutations that occur during replication.

• Mutagens are substances that mutate DNA, and carcinogens are substances that cause mutations that cause cancer.

• Mutations can be inherited, can occur during replication, and can be caused by mutagens or viruses.

• Mutations can be fixed by polymerase and DNA repair enzymes. We also have immune cells that kill mutated cells and some mutated cells will kill themselves by apoptosis


Summary

• Some inherited gene mutations that cause disease in humans include cystic fibrosis, Huntington’s, sickle-cell anemia, PKU, and nonpolyposiscolorectal cancer.

• Viruses that can cause cancer include HPV, HIV, hepatitis B or C, and EBV.


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Unit 1-DNA-stucture & Function-C08 Roscoe 1e PPT

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