Coordination of DNA single strand break repair.
Coordination of DNA single strand break repair.
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DOI：
10.1016/j.freeradbiomed.2016.11.039
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发表时间：
2017-06
影响因子：
7.4
通讯作者：
Wilson DM 3rd
中科院分区：
文献类型：
--
作者：
Abbotts R;Wilson DM 3rd
所有生物体的遗传物质都容易被修饰。在某些情况下，这些变化是被编程的，例如在减数分裂重组期间形成DNA双链断裂以产生配子多样性或类别转换重组以产生抗体多样性。然而，在大多数情况下，基因组损伤可能对生物体的健康有害，通过促进有害的细胞结果而导致疾病和衰老。一部分 DNA 修饰是由物理（即紫外线和电离辐射）和化学（如苯并芘、烷化剂、铂化合物和补骨脂素）等外源因素引起的，它们可以产生多种形式的 DNA 损伤，包括一系列“简单”和螺旋扭曲的碱基损伤、脱碱基位点、交联和各种类型的磷酸二酯链 休息。就频率而言，更重要的是内源性修饰机制，其中包括 DNA 化学键的水解分解、活性氧和正常细胞代谢的其他副产物的攻击，或不完全或必要的酶反应（例如拓扑异构酶或修复核酸酶）。外源和内源机制都与单链断裂的高风险相关，无论是直接产生还是作为 DNA 修复的中间体产生。本综述将重点关注单链断裂的产生、后果和解决，特别关注两种主要的协调修复蛋白：聚（ADP-核糖）聚合酶 1 (PARP1) 和 X 射线修复交叉互补蛋白 1 (XRCC1)。
The genetic material of all organisms is susceptible to modification. In some instances, these changes are programmed, such as the formation of DNA double strand breaks during meiotic recombination to generate gamete variety or class switch recombination to create antibody diversity. However, in most cases, genomic damage is potentially harmful to the health of the organism, contributing to disease and aging by promoting deleterious cellular outcomes. A proportion of DNA modifications are caused by exogenous agents, both physical (namely ultraviolet sunlight and ionizing radiation) and chemical (such as benzopyrene, alkylating agents, platinum compounds and psoralens), which can produce numerous forms of DNA damage, including a range of “simple” and helix-distorting base lesions, abasic sites, crosslinks and various types of phosphodiester strand breaks. More significant in terms of frequency are endogenous mechanisms of modification, which include hydrolytic disintegration of DNA chemical bonds, attack by reactive oxygen species and other byproducts of normal cellular metabolism, or incomplete or necessary enzymatic reactions (such as topoisomerases or repair nucleases). Both exogenous and endogenous mechanisms are associated with a high risk of single strand breakage, either produced directly or generated as intermediates of DNA repair. This review will focus upon the creation, consequences and resolution of single strand breaks, with a particular focus on two major coordinating repair proteins: poly(ADP-ribose) polymerase 1 (PARP1) and X-ray repair cross-complementing protein 1 (XRCC1).