DNA修复 (2)生物化学.pptVIP

DNA Repair DNA的损伤修复 突变与癌 (Mutation Cancer) 突变诱因 (Mutagens) 修复机制 (DNA repair systems) 修复系统缺损与疾病 (Diseases caused by impaired DNA repair systems) Mutations are linked to cancer Mutagens 化学诱变因素: 烷化剂、亚硝酸、嵌入剂； 物理诱变因素: 电离辐射(UV、X射线、?射线等宇宙射线)； Chemical and physical factors causing DNA injury Examples of chemical mutagens Formation of thymine dimer by UV DNA repairs systems 错配修复 (Mismatch repair) 碱基切除修复(Base-excision repair) 核苷酸切除修复 (Nucleotide-excision repair) 直接修复 (Direct repair) 重组修复与易错修复(recombination and error-prone repair) 应急反应（SOS response) Enzymes involved in DNA repair systems of E coli 大肠杆菌中错配修复主要依靠甲基化识别机制 甲基化位点引导错配位点识别 Excinuclease (uvrABC核酸酶)的作用机制 重组修复模型 应急反应导致大量基因表达，部分参与易错表达 Diseases with impaired DNA repair systems 切除修复缺损 着色性干皮病 (Xeroderma Pigmentosum Xp) 错配修复缺损 遗传性非息肉结肠癌 (Hereditary Nonpoly- posis Colorectal Cancer, HPCC) Brca1/Brca2基因缺损 乳腺癌高发 * A permanent change in the nucleotide sequence of DNA is called a mutation （在核酸序列上发生的永久性的变化叫突变）。 In mammals，there is a strong correlation between the accumu-lation of mutations and cancer。 Mutation, Mutant, Mutagenesis, Mutagen, Mutein (Mutain) Ames test for carcinogens 用一种携带了组氨酸合成途径中酶基因突变的沙门氏菌，检测化合物对该基因的恢复突变。 艾姆氏试验 大肠杆菌DNA复制过程中的甲基化 Base Modification 甲基化介导的错配修复机制 Base-excision repair mechanism in E coli Nucleotide-excision repair in E coli and homo sapiens Thymine dimer is repaired by photolyase 大肠杆菌photolyase的反应机制 O6-甲基鸟嘌啉更容易与T配对，会高频导致突变 O6-methylguanine-DNA methyltransferase 的半胱氨酸巯基接受甲基后自身永久失活，“舍己救人”的典范 Recombinational DNA repair / error-prone repair is activated when injury is severe Recombinational DNA repair has the same mechanism of DNA recombination during meiosis *