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Chapter 9 The Mutability and Repair of DNA

Chapter 9 The Mutability and Repair of DNA

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Chapter 9 The Mutability and Repair of DNA

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  1. Chapter 9 The Mutability and Repair of DNA 付翔2004生物学基地班10/8/2006

  2. Outline

  3. TheMutability • Low rates of mutation can drive evolution • High rates of mutation can be catastrophic

  4. TheSourcesofMutation • DNA replication errors • Chemical damage to the DNA • Insertion of transposons into genes (Chapter 11)

  5. TheChallengefortheCell • ScanthegenometodetecterrorsinsynthesisanddamagetotheDNA • MendthelesionsandrestoretheoriginalDNA

  6. TheNatureofMutations

  7. SomeReplicationErrorsEscapeProofreading

  8. MismatchRepairRemovesErrorsthatEscapeProofreading • Themismatchrepairsystemmustrapidlyfindandrepairmismatches • Itmustreplacethemisincorporatednucleotideinthenewlysynthesizedstrandandnotthecorrectnucleotideintheparentalstrand.

  9. MismatchRepairPathwayfortheRepairofReplicationErrors

  10. DammethylationinE.coli.

  11. SimilarPathwayinEukaryote • TheylackMutHandE.coli.’sclevertrickofusinghemimethylationtotagtheparentalstrand. • TheOkazakifragmentsplayanimportantrole.

  12. Abasic site, Apurinic site N-glycosyllinkage to the sugar HydrolysisandDeamination ThatiswhyDNAusesTinsteadofU. A and GAlso undergospontaneousdeamination 5-mC is common in vertebrate DNA, deamination productis a “natural” DNA base

  13. Alkylation,OxidationandRadiation These linked bases are incapable of base-pairing and cause stop during replication.

  14. BaseAnalogsandIntercalatingAgents

  15. RepairofDNADamage • Photoreactivation • ExcisionRepairSystem • RecombinationalRepair

  16. Photoreactivation

  17. Base Excision Repair

  18. DNA-glycosylase complex

  19. Excision Repair Pathway

  20. Recombination Repairs This is accomplished by the double-strand break(DSB) repair pathway. Although we generally consider recombination as an evolutionary device to explore new combinations of sequences, it may be that its original function was to repair damage in DNA.

  21. Translesion DNA Synthesis How do they switch remains unknown.

  22. Crystal Structure of a Translesion Polymerase

  23. Something about Translesion Synthesis Because of its high error rate, translesion synthesis can be considered a system of last resort. The translesion polymerase are expressed as part of a pathway known as the SOS response.