DNA Structure and Replication1 DNA Structure and Replication Chapter 14 (Chromatin, oncogenes & TSG in Chapter 10) Topics you are not responsible for: Section 14.5: eukaryote replication Section (p ) on ‘replisomes’ End of Chapter questions: Understand: all Apply: 1 – 6 & 8 Synthesize: 1 & 3 Do all mQuiz questions Do MolnQuiry Nucleic Acids Chapter

DNA Structure and Replication2 History of the discovery of the genetic material - 1? Bacteriophages infect Cells with DNA alone Alfred Hershey Martha Chase experiments radiolabeled DNA and protein HC-Experiment

DNA Structure and Replication3 History of the discovery of the genetic material - 2? P.A. Levene showed DNA is a polymer of nucleotides Erwin Chargaff showed DNA composition differs among organisms

DNA Structure and Replication4 What is the structure of a DNA strand? Nucleotides Phosphodiester linkages Sugar-Phosphate Bone 3’ to 5’ orientation

DNA Structure and Replication5 History of the discovery of the genetic material - 3? J. Watson, F. Crick, R. Franklin and M. Wilkins Determined the 3-D structure What did Franklin and Wilkins contribute? Crystalography What did Watson and Crick Contribute? -- Double helix -- Antiparallel orientation -- Base pairing

DNA Structure and Replication6 What is the structure of the DNA double helix? Complimentary base pairing -- base pairs are hydrogen bonded Antiparallel orientation Major and minor grooves Models

DNA Structure and Replication7 How does DNA replicate -1? Semiconservative replication The M. Meselson and F Stahl experiment MS-Experiment

DNA Structure and Replication8 How does DNA replicate -2? The need for RNA priming --”RNA Primase” Adding nucleotides -- “DNA Polymerase” 5’ to 3’ orientation Proofreading ability Nucleotide Polymerization Proofreading

DNA Structure and Replication9 How does DNA replicate -3? Origins of Replication Replication ‘forks’ Helicase DNA gyrase Replisomes

DNA Structure and Replication10 How does DNA replicate - 4? New strand 5 ‘  3’ orientation Leading & lagging strands DNA Helicase SS Binding protein RNA Primase DNA Polymerase III DNA Polymerase I Ligase Time DNA Replication

DNA Structure and Replication11 What is the structure of eukaryotic chromatin? (from chapter 10; page 190) Shape Structure of chromatin Nucleosomes Functional areas Centromeres Telomeres Replication Supercoiling Model

DNA Structure and Replication12 Sickle-cell anemia mutation What are mutations? -- see section chapter 20 section 20.2 Changes to the base sequence Some examples “Point Mutations” Base substitution Base deletion Base chemical change “Sequence mutations” Duplications Deletions Inversions “Chromosomal aberrations”

DNA Structure and Replication13 What types of chromosomal aberrations can occur? Deletions Translocations Duplications -- aneuploidy -- polyploidy Breakages What is the role of mutated tumor suppressor genes? -- detection & repair of DNA -- cell cycle control -- triggering of apoptosis Meningioma karyotype LOH - #17 Aneuploidy - #s 9, 7, and 20 Translocation/duplication - #s 2 and 6

DNA Structure and Replication14 How is DNA damage repaired? DNA polymerase “proofreading” Mutation detection -- tumor suppressor genes Excision repair (via endonuclease) Other repair enzymes photolyase  thymine dimers Excision Repair