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Diversity and accuracy of polymerases

Diversity and accuracy of polymerases. Multiple genes for replication in a typical eukaryotic genome, with and without intrinsic proofreading capacity Reverse transcriptases are particularly error prone

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Diversity and accuracy of polymerases

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  1. Diversity and accuracy of polymerases • Multiple genes for replication in a typical eukaryotic genome, with and without intrinsic proofreading capacity • Reverse transcriptases are particularly error prone • Base selectivity driven by conformation changes in polymerase (‘geometric selection’), rather than by nucleotide hydrogen bonding DNA pol l with nucleotide

  2. Two pathways of DNA repair

  3. DNA glycosylases – DNA repair enzymes

  4. Base removal and thymine dimers

  5. Structural bias toward transition substitutions in DNA

  6. DNA damage by reactive oxygen species (ROS)

  7. Pattern of spontaneous mutation, unaffected by selection

  8. Indels and their functional consequences

  9. Slipped-strand mispairing, a major mechanism of mutation

  10. Slipped strand mispairing in the ALL1 global regulator

  11. Anolismicrosatellite distribution shares characteristics of both mammals and reptiles ACACACACACACACACA……

  12. Increased germline mutation rate in humans living near Chernobyl

  13. Increased mutation rate at simple sequence repeats of Chernobyl barn swallows

  14. Jean-Baptiste Lamarck (1744-1829)

  15. Adaptive mutation? • NeoDarwinian paradigm - rate of adaptive mutation is independent of selective environment • Observation - increased rates of spontaneous ‘adaptive’ mutation (reversion) in cells originally not able to metabolize lactose • 1 bp frameshift mutation in lac operon is compensated by a -1 bp frameshift, usually in a mononucleotide repeat • Amplification of 10-40kb of the ‘leaky’ lac region 20-100 times

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