The SNM1A DNA repair nuclease.

The SNM1A DNA repair nuclease.
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DOI:
10.1016/j.dnarep.2020.102941
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发表时间:
2020-11
期刊:
影响因子:
3.8
通讯作者:
McHugh PJ
McHugh PJ
中科院分区:
医学3区
文献类型:
--
作者:
Baddock HT;Yosaatmadja Y;Newman JA;Schofield CJ;Gileadi O;McHugh PJ

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未修复或错误修复的DNA损伤可能导致许多病症或疾病状态的发病机制;因此,DNA损伤修复途径及其内的蛋白质是保护基因组所必需的。人SNM 1A是一种5′-to-3′外切核酸酶,在多种DNA损伤修复过程中发挥作用。迄今为止,大多数数据表明SNM 1A在主要ICL修复中的作用:SNM 1A缺陷细胞表现出对ICL诱导剂(例如丝裂霉素C和顺铂)的超敏反应;体内和体外实验都证明SNM 1A和XPF-ERCC 1可以在ICL修复的“脱钩”步骤中一起起作用。SNM 1A还与许多其他蛋白质相互作用,这些蛋白质有助于典型ICL修复之外的基因组完整性(例如PCNA和CSB),并且这些蛋白质可能在调节SNM 1A功能、亚细胞定位和翻译后修饰状态中发挥作用。这些数据还提供了SNM 1A可能有助于的其他DNA修复途径的进一步见解。这篇综述旨在讨论核酸外切酶SNM 1A的各个方面及其对DNA损伤耐受的贡献。
Unrepaired, or misrepaired, DNA damage can contribute to the pathogenesis of a number of conditions, or disease states; thus, DNA damage repair pathways, and the proteins within them, are required for the safeguarding of the genome. Human SNM1A is a 5′-to-3′ exonuclease that plays a role in multiple DNA damage repair processes. To date, most data suggest a role of SNM1A in primarily ICL repair: SNM1A deficient cells exhibit hypersensitivity to ICL-inducing agents (e.g. mitomycin C and cisplatin); and both in vivo and in vitro experiments demonstrate SNM1A and XPF-ERCC1 can function together in the ‘unhooking’ step of ICL repair. SNM1A further interacts with a number of other proteins that contribute to genome integrity outside canonical ICL repair (e.g. PCNA and CSB), and these may play a role in regulating SNM1As function, subcellular localisation, and post-translational modification state. These data also provide further insight into other DNA repair pathways to which SNM1A may contribute. This review aims to discuss all aspects of the exonuclease, SNM1A, and its contribution to DNA damage tolerance.
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