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Molecular Basis of Inheritance
Chapter 16
DNA as Genetic Material
• Watson and Crick – 1st scientists to propose structure of DNA - responsible for transmission of traits from 1 generation to next.
• Requires precise transmission occurs.
http://www.ncbe.reading.ac.uk/DNA50/Resources/wc1993.gif
• Griffith - injected live bacterial strains into mice.
• Mixed R strain of bacteria (harmless) with heat-killed S strain (harmful) and injected it.
• After mouse died, removed strain from mouse.
http://www.virtuallaboratory.net/Biofundamentals/lectureNotes/AllGraphics/Griffith.jpg
• Transformation - change in genotype and phenotype due to assimilation of foreign substance (now DNA) by cell.
• Substance found to be DNA - supported by injecting bacteria into viruses.
• Viruses consist of DNA (sometimes RNA) enclosed by protective coat of protein.
http://www.monografias.com/trabajos5/virus/Image164.gif
• To replicate - virus infects host cell; takes over cell’s metabolic machinery.
• Viruses that specifically attack bacteria - bacteriophages (phages)
• Hershey and Chase labeled protein and DNA - injected them into bacteria.
http://www.swbic.org/products/clipart/images/bacteriophage.jpg
• Hershey and Chase concluded that injected DNA of phage provides genetic information that makes infected cells produce new viral DNA and proteins, which assemble into new viruses.
• DNA doubles prior to mitosis.
• By 1940’s - discovered that DNA was made of bases.
• Adenine, thymine, cytosine, and guanine.
• Chargaff’s rules - an even amount of thymine and adenine. (and guanine and cytosine)
http://fig.cox.miami.edu/~cmallery/150/gene/BasePairing.gif
• Was known that sugar of one nucleotide attached to phosphate of another - forms backbone of DNA.
• Watson 1st to figure out that DNA was in helix shape + specific distance between nucleotides.
• Partnered with Crick – came up with double stranded model of DNA - double helix.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Fig. 16.5
• Found that purine has to pair with pyrimidine to achieve distance needed.
• Knew that adenine always paired with thymine and cytosine always with guanine.
• Discovered that bases were held together by hydrogen bonds.
• Adenine forms 2 hydrogen bonds
only with thymine; guanine forms 3 hydrogen bonds only with cytosine.
• Each gene found to have unique sequence of nitrogen bases - DNA strands not all the same.
http://academy.d20.co.edu/kadets/lundberg/dna_wallpaper/dna800x600.jpg
DNA Replication and Repair
• Watson and Crick discovered each strand of DNA can make template to make more DNA.
• Cell copies DNA - each strand forms as template to determine new complementary bases.
• Nucleotides pair in complementary fashion, one by one.
• Happens by semiconservative replication - each DNA molecule has one parent strand and one daughter strand.
• Idea later supported through bacteria studies.
• This
• Even though process is amazingly quick, only about 1 in a billion nucleotides copied wrong.
• Proteins and enzymes also part of process, not just nucleotides.
http://www.bio.miami.edu/dana/250/nucleotides.jpg
• Origins of replication - where replication process begins.
• Bacteria - 1 site - replication looks like bubble moving along DNA.
• Eukaryotes - many origins of replication on each chromosome.
• Origin sites - DNA strands separate forming replication “bubble” with replication forks at each end.
• Elongation of DNA catalyzed by DNA polymerase.
• Polymerase adds complementary bases to growing strand of new DNA.
• Strands of DNA - antiparallel.• Sugar-phosphate backbones run
in opposite directions.• Each end of strand labeled either
5’ end or 3’ end.
• Nucleotides only be added to 3’ end.
• DNA strand can only elongate from 5’ end to 3’ end.
• Replication fork - problem - system because strands run in opposite directions (antiparallel)
http://www.mie.utoronto.ca/labs/lcdlab/biopic/fig/11.16.jpg
• 1 parent strand (leading strand - one that runs 3’ to 5’) used as template to keep complementary strand continuous.
• Other strand (lagging strand - one that runs 5’ to 3’) copied from fork in small segments - Okazaki fragments.
http://www.biology.arizona.edu/molecular_bio/problem_sets/nucleic_acids/graphics/repfork1.gif
• Fragments “glued” together by DNA ligase to form backbone (made of sugar and phosphate) of single DNA strand.
• Polymerase adds nucleotides to strands, cannot start whole process.
• Done by a piece of RNA - primer.• Primase links ribonucleotides
that are complementary to DNA template into primer.
http://www.biologie.uni-hamburg.de/b-online/library/bio201/primase.jpg
• Once primer formed, polymerase can add DNA nucleotides to growing daughter strand of DNA.
• Later - different DNA polymerase replaces original RNA with new complementary DNA nucleotides - there is no RNA left in strand.
• Helicase - untwists double helix of DNA at replication fork.
• Single-strand binding proteins help keep strands apart from one another during replication.
• At replication fork, leading strand copied continuously into fork from single primer.
• Lagging strand copied away from fork in short segments, each requiring new primer.
• Original errors in reading of template occur.
• Enzyme (DNA polymerase) removes mistake and replaces it.
• Some things can alter DNA outside of body.
http://library.thinkquest.org/C0123260/basic%20knowledge/images/basic%20knowledge/DNA/polymerase%201.jpg
• X-rays and UV rays can alter DNA after replication.
• Mistakes can be fixed after DNA synthesis because cell continually monitors DNA.
• Mismatch repair, special enzymes fix incorrectly paired nucleotides - happens in certain types of cancers.
http://www.sinauer.com/cooper4e/sample/Figures/Chapter%2006/highres/CELL4e-Fig-06-24-0.jpg
• Nucleotide excision repair, nuclease cuts out segment of damaged strand.
• Xeroderma pigmentosa (genetic disease) cannot go through process.
• Disease prevents person from going in sun because UV rays interfere with DNA replication.
• More susceptible to skin cancer because they cannot fix mistakes.
http://162.129.70.33/images/xeroderma_pigmentosa_2_040620.jpg
• Limitations in DNA polymerase create problems for linear DNA of eukaryotic chromosomes.
• Ends of DNA strand can break down from constant replication.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Fig. 16.18
• Ends of eukaryotic chromosomal DNA molecules – telomeres - special nucleotide sequences.
• Telomeres protect genes from being eroded through multiple rounds of DNA replication.
• When telomeres shorten, telomerase uses piece of RNA to lengthen telomere.
• Telomerase not present in all cells - life span to certain tissues or organism itself.
• Important for telomerase to be present in gamete cells so they can pass long telomeres on to zygote.
• Active telomerase in body cells can be responsible for cancer cells because cells keep dividing.