The MOLECULAR Basis of Inheritance. n Structure & Function!!!

Searching for Genetic Material, I n Mendel: modes of heredity in pea plants n Morgan: genes located on chromosomes n Griffith: bacterial work; transformation: change in genotype and phenotype due to assimilation of external substance (DNA) by a cell n Avery: transformation agent was DNA

Searching for Genetic Material, II n Hershey and Chase used bacteriophages (phages)to deduce that: –√ DNA (not protein) is the hereditary material n Experiment: sulfur(S) is in protein, phosphorus (P) in DNA; only P was found in host cell

DNA Structure n Chargaff ratio of nucleotide bases (A=T; C=G) n Watson & Crick (Wilkins, Franklin) n The Double Helix √ nucleotides: nitrogenous base (thymine, adenine, cytosine, guanine); sugar deoxyribose; phosphate group

DNA Bonding n Purines: ‘A’ & ‘G’ n Pyrimidines: ‘C’ & ‘T’ (Chargaff rules) n ‘A’ H + bonds (2) with ‘T’ n ‘C’ H + bonds (3) with ‘G’ n Van der Waals attractions between the stacked pairs

DNA Structure Campbell Animation

DNA Replication n Watson & Crick strands are complementary; nucleotides line up on template according to base pair rules (Watson) n Meselson & Stahl replication is semiconservative; Expt: varying densities of radioactive nitrogen Meselsen/Stahl Animation

DNA Replication: 500 nucleotides/sec!! n Begin at “Origins of replication” –A specific sequence of nucleotides; 1000s per chromosome n Replication forks open to form “replication bubbles”. n 2 main stages: Separation & Synthesis n Separation: –Helicase:catalyzes the untwisting of the DNA at the replication fork –Single Strand Binding Proteins: hold the helix open n Synthesis: –DNA polymerase:catalyzes the elongation of new DNA

By the way, DNA has an…. n Antiparallel nature: n sugar/phosphate backbone runs in opposite directions n one strand runs 5’ to 3’, while the other runs 3’ to 5’ n DNA polymerase only adds nucleotides at the free 3’ end, forming new DNA strands in the 5’ to 3’ direction only

Synthesis: n Initiation: Primer (short RNA sequence is attached first with “primase”) n DNA Polymerase then attaches each new nucleotide to the growing strand using “nucleoside triphosphate” n DNA Pol can only add 5’ to 3’ so… n Leading strand: synthesis toward the replication fork is “continuous (5’ to 3’ direction from the 3’ to 5’ master strand) n Lagging strand: synthesis away from the replication fork is discontinuous. n Okazaki fragments; joined by DNA ligase (must wait for 3’ end to open; again in a 5’ to 3’ direction)

DNA Replication n

DNA Repair n Mismatch repair: DNA polymerase n Excision repair: Nuclease n Telomere ends: telomerase

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