DNA损伤与修复课件.pptx

DNA損傷與修復

DNADAMAGEANDREPAIR

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DeoxyribonucleicAcid（DNA）

;Base;Pyrimidine（嘧啶）;Nucleoside（核苷）;Nucleotide（核苷酸）

;;DNADamage;DNA損傷的原因和後果;DNA複製誤差;堿基錯配;自主突變;Singlebasechange

;06_23_Depurination.jpg;Depurination

Thebondlinkingbasetosugarweekened,iseasytobreak.;物理因素引起的DNA損傷;TT，CC，TC二聚體;1.Ultravioletirradiation

A-TbecameT-T;電離輻射引起DNA損傷;電離輻射的直接和間接作用;DNA鏈斷裂;化學因素引起的DNA損傷;化學因素引起的DNA損傷;Alkylation（烷基化）

-CH3wasaddedtoDNAbases.;Viruses

ThereplicationofdamagedDNAbeforecelldivisioncanleadtotheincorporationofwrongbasesoppositedamagedones.DaughtercellsthatinheritthesewrongbasescarrymutationsfromwhichtheoriginalDNAsequenceisunrecoverable(exceptintherarecaseofabackmutation,forexample,throughgeneconversion).;DNA損傷的後果;DNARepair;DNArepair

;RepairingDamagedBases;Directrepair

;;BasicmechanismOfRepairingDNA

;BaseExcisionRepair

;DNArepairbybaseexcision;NucleotideExcisionrepair（NER）

;NucleotideExcision;Nucleotideexcisionrepair

;Mismatchrepair

;Mismatchrepairsystem;MismatchRepair(MMR);HowdoestheMMRsystemknowwhichistheincorrectnucleotide?;Theassumedmechanismsformismatchrepair.MismatchesaredetectedbyadimerofthemismatchrepairproteinMutS(encodedbyMSH2).MutL(encodedbyMLH1)hasweakATPaseactivityanditisalsoshowntobeaDNAendonucleasesameasMutH.TheentireMutSHLcomplexthenslidesalongtheDNAinthedirectionofthemismatch,liberatingthestrandtobeexcisedasitgoes.Anexonucleasetrailsthecomplexanddigeststhess-DNAtail

;ProteinsinvolvedintheDNArepairingofE.coli.

;RecombinationalRepair;PostreplicationRepair(recombinationalDNArepair)?;RecombinationalExcisionRepair;Recombinationrepair

;;AnassumedmechanismfortherepairofDNAdouble-strandbreaksbyhomologousrecombination(HR).HRutilizesahomologousstretchonasisterchromatidtoaccuratelyr