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DNA Structure and Function DNA explains it all • Explains HOW chromosomes pass on genes • Chemical instructions for building proteins • Understanding structure explains function Recent understanding Understanding genetic material • Originally thought that proteins were genetic material – Diverse group of molecules – Specific functions • Didn’t know much about nucleic acids – Small and uniform molecules Model organisms • Bacteria and Viruses – Small genome – Easily manipulated – Prone to mutations – Share genetic material Viruses • • • • Protein Coat DNA/RNA Hijack host cell Transform 1928-Transformation Fredrick Griffith 1952-Genetic material Hershey-Chase Structural model of DNA • Race to come up with a model • Watson and Crick compiled research from different labs • Used chemistry to make guesses about bonds 1950s-Chargaff’s rules • % Adenine = % Thymine • % Cytosine = %Guanine 1950s-Rosalind Franklin • X-ray crystallography Double Helix • Sugar Phosphate backbone • Paired nucleotides • Hydrogen bonds hold bases together Nucleotides Base Pairing • Complimentary bases allows replication and repair 3 models of replication 1958-Meselson and Stahl • Switched between normal and heavy nitrogen media • New DNA strands were heavier than old DNA Replication • Semi-conservative • Each strand is a template for new DNA Origin of Replication • Enzymes recognize site, separate strands of DNA – Bacteria have single, circular plasmid, one origin – Chromosomes have many sites Elongation • DNA polymerases align nucleotides with complimentary bases Anti-parallel • Anti-parallel= strands run in opposite directions • Two different “ends” to nucleotide 5` 3` • • • • Can only add new nucleotides to 3` end Strand grows 5`3` Leading strand Lagging Strand – Okazaki fragments Primers • • • • Polymerase can only add to existing chain RNA Primer is created as a foundation Leading strand needs one primer Lagging strand needs a primer for each segment • RNA is then replaced by DNA The enzymes • • • • Primase- creates RNA primer DNA polymerase III- adds nucleotides DNA polymerase I- replaces RNA primer DNA ligase- bonds Okazaki fragments together • Helicase- untwists and separates strands Replication Machine • Replication enzymes form a large complex • Complex anchors to nuclear matrix • DNA moves through enzymes Proofreading DNA • 1 error/ 100,000 base pairs • Polymerases identify and remove mismatched nucleotides • Defect in mismatch repair enzymes is linked to cancer • Errors are reduced to 1/10 billion Repairing DNA • Nucleotide excision • Thymine Dimers – UV radiation – Xeroderma pigmentosa Telomeres • No way to replace RNA primer at the 3` end of chromosome (no 3` to attach on to) • Each round of replication results in a shorter chromosome • Telomeres = repeated TTAAGGG • Protect necessary genes from being eroded Aging • Telomeres shorten each time a cell divides • Once cell exhausts telomeres it dies • Telomerase=enzyme that restores telomeres – Active in germ line cells – Detected in cancer cells