第2节dna的化学损伤及其PPT.pptVIP

第2节DNA的化学损伤及其修复; 嘌呤;1.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→U U:A ?A→H H:C ?G→X X:C;1.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;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:T 1.2.2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:A;2.DNA损伤的直接逆转 (direct reversal of DNA damage) 2.1光激活作用（photoreactivation） ?DNA光解酶（DNA photolyase）;2.DNA损伤的直接逆转 (direct reversal of DNA damage) 2.2甲基转移酶（methyltransferase）;3.切除修复 (excision repair) 3.1碱基切除修复（base excision repair） 3.2核苷酸切除修复（nucleotide excision repair）;3.切除修复 (excision repair) 3.1碱基切除修复（base excision repair） 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;3.切除修复 (excision repair) 3.1碱基切除修复（base excision repair） 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;3.切除修复 (excision repair) 3.1.1修复过程（base excision repair） 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;3.切除修复 (excision repair) 3.1碱基切除修复（base excision repair） 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;The majority of oxidatively damaged DNA bases are substrates for two overlapping pathways: DNA glycosylase-initiated base excision repair (BER) and apurinic/apyrimidinic (AP) endonuclease-mediated nucleotide incision repair (NIR) . In the NIR pathway, an AP endonuclease makes an incision 5′ to a damaged nucleotide and then extends the resulting single-strand break to a gap by a nonspecific 3′→5′ exonuclease activity. AP endonucleases are multifunctional DNA repair enzymes that possess AP site nicking, 3′ repair diesterase, NIR, and 3′→5′exonuclease activities;;Spontaneous hydrolytic deamination of cytosine to uracil (U) in DNA is a constant source of genome instability in cells. This mutagenic process is greatly enhanced at high temperatures and in single-stranded DNA. If not repaired, these uracil residues give rise to C→T transitions, which are the most common spontaneous mutations occurring in living organisms