A Quick Review DNA The Molecular Basis of Inheritance

Scientific History Road to understanding that DNA is the genetic material T.H. Morgan (1908): genes are on chromosomes Frederick Griffith (1928)- Mice, S strain and R strain a transforming factor can change phenotype Avery, McCarty & MacLeod (1944) transforming factor is DNA Erwin Chargaff (1947) Chargaff rules: A = T, C = G Hershey & Chase (1952) T2 bacteriophage, S into Proteins and P into DNA confirmation that DNA is genetic material Watson & Crick (1953) R. Franklin? determined double helix structure of DNA Meselson & Stahl (1958) semi-conservative replication

Different Base Pairs Purines Nitrogen bases made of double rings of carbon and nitrogen atoms Adenine (A) and Guanine (G)

Different Base Pairs Pyrimidines Nitrogen bases made of single ring of carbon and nitrogen atoms Cytosine (C) and Thymine (T)

Watson and Crick Purine + purine: too wide Pyrimidine + pyrimidine: too narrow Purine + pyrimidine: width consistent with X-ray data Watson Crick

DNA Bonding Covalent bonds: Sugars to nitrogen bases Hydrogen Bonds: (A) bonds (2) with (T); (C) bonds (3) with (G) Van der Waals Bonds attractions between the stacked pairs Phosphodiester Bonds between phosphate of one nucleotide to the sugar of another

DNA Replication Leading strand Lagging strand Origin of replication Overall direction of replication Leading strand Lagging strand Origin of replication Lagging strand Leading strand OVERVIEW DNA pol III Leading strand DNA ligase Replication fork 5¢ DNA pol I 3¢ Primase Parental DNA DNA pol III Lagging strand Primer 3¢ 5¢

DNA polymerases DNA polymerase III 1000 bases/second! main DNA builder editing, repair & primer removal In 1953, Kornberg was appointed head of the Department of Microbiology in the Washington University School of Medicine in St. Louis. It was here that he isolated DNA polymerase I and showed that life (DNA) can be made in a test tube. In 1959, Kornberg shared the Nobel Prize for Physiology or Medicine with Severo Ochoa — Kornberg for the enzymatic synthesis of DNA, Ochoa for the enzymatic synthesis of RNA. DNA polymerase III enzyme

Excision Repair Thymine dimer is a mismatch mutation caused by adjacent thymines not correctly base-pairing with their complementary adenines Mismatch repair done by special enzymes fix incorrectly paired nucleotides. A hereditary defect in one of these enzymes is associated with a form of colon cancer. Nucleotide excision repair Nuclease enzymes cuts out a segment of a damaged strand. The gap is filled in by DNA polymerase and ligase.

Causes of Mutations DNA constantly subject to potentially harmful chemical and physical agents. Mutagen - physical and chemical agents that change DNA Reactive chemicals, radioactive emissions, X-rays, and ultraviolet light can change nucleotides DNA bases often undergo spontaneous chemical changes under normal cellular conditions. Mismatched nucleotides that are missed by DNA polymerase or mutations that occur after DNA synthesis is completed can often be repaired. Each cell continually monitors and repairs its genetic material, with over 130 repair enzymes identified in humans.

Telomeres Repeating, non-coding sequences at the end of chromosomes = protective cap limit to ~50 cell divisions; Human telomeres sequence is typically TTAGGG repeated 100 to 1,000 times. Telomerase enzyme extends telomeres by using RNA as a template can add DNA bases at 5 end different level of activity in different cells high in stem cells & cancers

Telomere Extension 11 min introduction **commercial warning** https://www.youtube.com/watch?v=AJNoTmWsE0s 2 min https://www.youtube.com/watch?v=qQCecSuPa1w 1 min animation https://www.youtube.com/watch?v=8_bNfQd7Smc 3 min https://www.youtube.com/watch?v=m3qqUy880dQ 11 min introduction **commercial warning** https://www.youtube.com/watch?v=BkcXbx5rSzw 2 min