分子生物学（张海红）9 章.pptVIP

DNA damage and their repair Causes Repair Direct reversal of DNA damage Base excision repair Nucleotide excision repair Recombination (DSB) repairs Translesion DNA synthesis damage spontaneously alkylation, oxidation and radiation base analogs intercalating agents 诱变剂的种类 1.260紫外辐射：环丁二聚 2.电离辐射 3.加热:A-P位点 化学诱变剂 1.碱基类似物： 5-溴尿嘧啶 2.脱氨剂：腺嘌呤——次黄嘌呤 3.烷化剂：甲基磺酸乙脂(EMS) 4.嵌入剂：EB 物理诱变剂 Chapter 9 If DNA naturally contained uracil instead of thymine, the deamination of cytosine will create a natrual base uracil which the repair system will not easily recognize. Can 5-mC ? T lesion be repaired? Why DNA contains T instead of U? Chapter 9 2. Alkylation, Oxidation and Radiation DNA is subject to attack from Reactive oxygen species (O2-, H2O2, OH?) Figure 9-8 G modification Alkylating chemical: Nitrosamines (亚硝胺) “O2-” hyperoxide “H2O2” Peroxide “OH?” hydroxyl Chapter 9 UV(紫外线) induces a cyclobutane between adjacent thymines Figure 9-9 Thymine dimer. 相邻两个嘧啶之间发生光化学聚合, 形成胸腺嘧啶二聚体(环丁烷环)。 Gamma radiation and X-rays (ionizing radiation) cause double-strand breaks and are particularly hazardous (hard to be repaired). Chapter 9 3. Base analogs (碱基类似物) and intercalating agents (嵌入剂) Base analogs: similar enough to the normal bases to be processed by cells and incorporated into DNA during replication. But they base pair differently, leading to mistake during replication. The most mutagenic base anolog is 5-bromouracil (5-BrU) (溴尿嘧啶), an anolog of thymine. Chapter 9 Chapter 9 5-bromouracil, base anolog of thymine, can mispair with guanine Figure 9-10a Base analogues 烯醇异构体 酮异构体 A:T ? C:G Chapter 9 Intercalating agents Intercalating agents are flat molecules containing several polycyclic rings that interact with the normal bases in DNA through hydrogen bonds and base stacking. 溴乙非啶 二氨基吖啶/原黄素 吖啶, 氮蒽 Figure 9-10b Base analogues Chapter 9 Section 3: Repair of DNA Damage Some damages, such as thymine dimer, nick or breaks in the DNA backbone, create impediments to replication o