Controlling the efficiency of excision repair
Controlling the efficiency of excision repair
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DOI：
10.1016/s0921-8777(00)00071-9
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发表时间：
2001-02-25
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影响因子：
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通讯作者：
Hanawalt, PC
中科院分区：
文献类型：
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作者：
Hanawalt, PC
回顾了早期的研究，这些研究导致了普遍存在的 DNA 切除修复过程的发现，随后回顾了转录偶联修复 (TCR) 和全局基因组核苷酸切除修复 (GGR) 的途径。通过使用 5-溴尿嘧啶对新合成的 DNA 进行密度标记，发现了紫外线照射细菌中受损 DNA 的修复复制。然后将该测定法用于人类细胞，以验证非计划 DNA 合成现象作为切除修复的衡量标准，并阐明 DNA 修复障碍的第一个例子，着色性干皮病。 TCR 通路的特征（在科凯恩综合征 (CS) 中存在缺陷）包括在未受损 DNA 的转录暂停位点出现“无端 TCR”的可能性。研究表明，GGR 通路是通过大肠杆菌中的 SOS 应激反应和人类细胞中 p53 肿瘤抑制基因的激活产物来控制的。这些调节系统特别影响主要紫外线诱导光产物环丁烷嘧啶二聚体以及化学致癌物加合物（例如苯并（a）芘二醇-环氧化物）的修复效率。啮齿动物细胞（通常缺乏 p53 控制的 GGR 途径）和肿瘤病毒感染的人类细胞（p53 功能被废除）无法对某些病变进行有效的 GGR。因此，在解释遗传毒理学风险评估系统的结果时应谨慎。切除修复中的许多问题仍有待解决，包括扫描DNA损伤的机制和修复工厂的亚细胞定位。当复制叉遇到模板 DNA 中的损伤时，关于修复、重组和跨损伤合成的多种选择也一直存在问题。四十年前，DNA 切除修复领域开始研究紫外线照射细菌中 DNA 合成的恢复。 (C) 2001 Elsevier Science B.V. 保留所有权利。
The early studies are recounted, that led to the discovery of the ubiquitous process of DNA excision repair, followed by a review of the pathways of transcription-coupled repair (TCR) and global genomic nucleotide excision repair (GGR). Repair replication of damaged DNA in UV-irradiated bacteria was discovered through the use of 5-bromouracil to density-label newly synthesized DNA. This assay was then used in human cells to validate the phenomenon of unscheduled DNA synthesis as a measure of excision repair and to elucidate the first example of a DNA repair disorder, xeroderma pigmentosum. Features of the TCR pathway (that is defective in Cockayne syndrome (CS)) include the possibility of "gratuitous TCR" at transcription pause sites in undamaged DNA. The GGR pathway is shown to be controlled through the SOS stress response in E. coli and through the activated product of the p53 tumor suppressor gene in human cells. These regulatory systems particularly affect the efficiency of repair of the predominant UV-induced photoproduct, the cyclobutane pyrimidine dimer, as well as that of chemical carcinogen adducts, such as benzo(a)pyrene diol-epoxide. Rodent cells (typically lacking the p53-controlled GGR pathway) and tumor virus infected human cells tin which p53 function is abrogated) are unable to carry out efficient GGR of some lesions. Therefore, caution should be exercised in the interpretation of results from such systems for risk assessment in genetic toxicology. Many problems in excision repair remain to be solved, including the mechanism of scanning the DNA for lesions and the subcellular localization of the repair factories. Also there are persisting questions regarding the multiple options of repair, recombination, and translesion synthesis when replication forks encounter lesions in the template DNA. That is where the field of DNA excision repair began four decades ago with studies on the recovery of DNA synthesis in UV-irradiated bacteria. (C) 2001 Elsevier Science B.V. All rights reserved.