dna的化学损伤及其

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1、第2节DNA的化学损伤及其修复嘌呤腺嘌呤Ade6-氨基嘌呤鸟嘌呤Gue2-氨基-6-氧嘌呤嘧啶胞嘧啶Cyt2-氧-4-氨基嘧啶尿嘧啶Ura2,4-二氧嘧啶胸腺嘧啶Thy5-甲基-2,4-二氧嘧啶碱基124NN3561357NNNNCH24689HNNNNCHNH2HNNNNCHOHH2NNNNH2OHNNOONNOOCH31.DNA的损伤1.1DNA的自发损伤：水解和脱氨基作用1.1.1脱氨基作用C→UU:AA→HH:CG→XX:CP2691.DNA的损伤1.1DNA的自发损伤：水解和脱氨基作用1.1.2脱碱基P269

2、1.DNA的损伤1.2DNA的损伤：烷化反应、氧化反应和辐射1.2.1烷化反应G甲基化为O6-甲基鸟嘌呤，与T配对。G:C转换为A:T1.2.2氧化反应鸟嘌呤氧化为氧代鸟嘌呤(oxoG)，可与A或C配对G:C颠换为T:AP2691.DNA的损伤1.2DNA的损伤：烷化反应、氧化反应和辐射1.2.3辐射紫外线电离辐射P2691.DNA的损伤1.3DNA的损伤：碱基类似物和嵌入剂碱基类似物嵌入剂P2712.DNA损伤的直接逆转(directreversalofDNAdamage)2.1光激活作用（photoreact

3、ivation）DNA光解酶（DNAphotolyase）P2732.DNA损伤的直接逆转(directreversalofDNAdamage)2.2甲基转移酶（methyltransferase）P2733.切除修复(excisionrepair)3.1碱基切除修复（baseexcisionrepair）3.2核苷酸切除修复（nucleotideexcisionrepair）3.切除修复(excisionrepair)3.1碱基切除修复（baseexcisionrepair）①DNA糖基化酶识别错误碱基并将其除去，形成脱

4、氧戊糖②AP核酸内切酶切除脱碱基戊糖③DNA聚合酶I以未受损的DNA链为模板合成新链，DNA连接酶连接新链P2743.切除修复(excisionrepair)3.1碱基切除修复（baseexcisionrepair）3.1.1修复过程①DNA糖基化酶识别错误碱基并将其除去，形成脱氧戊糖P2743.切除修复(excisionrepair)3.1.1修复过程（baseexcisionrepair）②AP核酸内切酶和核酸外切酶切除脱碱基戊糖③DNA聚合酶I以未受损的DNA链为模板合成新链，DNA连接酶连接新链P2743.切除修复(

5、excisionrepair)3.1碱基切除修复（baseexcisionrepair）3.1.1修复过程①DNA糖基化酶识别错误碱基并将其除去，形成脱氧戊糖②AP核酸内切酶和核酸外切酶切除脱碱基戊糖③DNA聚合酶I以未受损的DNA链为模板合成新链，DNA连接酶连接新链P274ThemajorityofoxidativelydamagedDNAbasesaresubstratesfortwooverlappingpathways:DNAglycosylase-initiatedbaseexcisionrepair(BER)a

6、ndapurinic/apyrimidinic(AP)endonuclease-mediatednucleotideincisionrepair(NIR).IntheNIRpathway,anAPendonucleasemakesanincision5′toadamagednucleotideandthenextendstheresultingsingle-strandbreaktoagapbyanonspecific3′→5′exonucleaseactivity.APendonucleasesaremultifuncti

7、onalDNArepairenzymesthatpossessAPsitenicking,3′repairdiesterase,NIR,and3′→5′exonucleaseactivitiesSpontaneoushydrolyticdeaminationofcytosinetouracil(U)inDNAisaconstantsourceofgenomeinstabilityincells.Thismutagenicprocessisgreatlyenhancedathightemperaturesandinsingle

8、-strandedDNA.Ifnotrepaired,theseuracilresiduesgiverisetoC→Ttransitions,whicharethemostcommonspontaneousmutationsoccurringinlivingorganismsandaref