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chapter9themutabilityandrepairofdna(文件)

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【正文】 repaired? Vertebrate DNA frequently contains 5methyl cytosine in place of cytosine as a result of the action of methyl transferase. This modified base plays a role in the transcriptional silencing (Ch 17). DNA is damaged by alkylation (烷基化 ), oxidation (氧化 ) and radiation (輻射 ) DNA damage Figure 98 G modification Alkylating chemical: Nitrosamines (亞硝胺 ) Reactive oxygen species (O2, H2O2, OH?) “ O2” hyperoxide “ H2O2” Peroxide “ OH?” hydroxyl Figure 99 Thymine dimer. UV induces a cyclobutane (環丁烷 ) ring between adjacent T. Radiation damage 1 Gamma radiation and Xrays (ionizing radiation) cause doublestrand breaks and are particularly hazardous (hard to be repaired). Radiation damage 2 Mutations are also caused by base analogs (堿基類似物 ) and intercalating agents (嵌入劑 ) DNA damage ?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 mispairing during replication. ?The most mutagenic base analog is 5bromoUracil (5BrU) (溴尿嘧啶 ). Figure 910a Base analogues Figure 333 GU pair 烯醇異構體酮異構體 ?Intercalating agents are flat molecules containing several polycyclic rings that interact with the normal bases in DNA through hydrogen bonds and base stacking. Figure 910b Intercalating agents 溴乙非啶二氨基吖啶 /原黃素吖啶 , 氮蒽 Topic 3: Repair of DNA damage CHAPTER 9 The mutability and repair of DNA 3/22/05 Two consequence of DNA damage ? Some damages, such as thymine dimer, nick or breaks in the DNA backbone, create impediments to replication or transcription ? Some damages creates altered bases that has no effect on replication but cause mispairing, which in turn can be converted to mutation. Repair of DNA damage ?Direct reversal of DNA damage by photoreactivation (光活化作用 ) and alkyltransferase (烷基轉移酶 ) ?Base excision repair (切割修復 ) ?Nucleotide excision repair ?Rebination (DSB) repairs ?Translesion DNA synthesis Mechanisms to repair a damage See Table 91 for summary Repair of DNA damage Direct reversal of DNA damage Errorfree repair Repair of DNA damage Photoreactivation Figure 911 Monomerization of thymine dimers by DNA photolyases in the presence of visible light. Methyltransferase Removes the methyl group from the methylated O6methylguanine. The methyl group is transferred to the protein itself, inactivating the

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