Life Sciences Institute, Zhejiang University, Hangzhou, 310058, Zhejiang, China,
Cell Mol Life Sci. 2014 Oct;71(19):3779-97. doi: 10.1007/s00018-014-1649-5. Epub 2014 May 25.
Exogenous and endogenous genotoxic agents, such as ionizing radiation and numerous chemical agents, cause DNA double-strand breaks (DSBs), which are highly toxic and lead to genomic instability or tumorigenesis if not repaired accurately and efficiently. Cells have over evolutionary time developed certain repair mechanisms in response to DSBs to maintain genomic integrity. Major DSB repair mechanisms include non-homologous end joining and homologous recombination (HR). Using sister homologues as templates, HR is a high-fidelity repair pathway that can rejoin DSBs without introducing mutations. However, HR execution without appropriate guarding may lead to more severe gross genome rearrangements. Here we review current knowledge regarding the factors and mechanisms required for accomplishment of accurate HR.
外源性和内源性遗传毒性剂,如电离辐射和许多化学制剂,会导致 DNA 双链断裂(DSBs),如果不能准确有效地修复,DSBs 会产生高度毒性并导致基因组不稳定或肿瘤发生。细胞在进化过程中已经发展出某些修复机制来应对 DSBs,以维持基因组完整性。主要的 DSB 修复机制包括非同源末端连接和同源重组(HR)。HR 利用姐妹同源物作为模板,是一种高保真的修复途径,可在不引入突变的情况下重新连接 DSB。然而,没有适当保护的 HR 执行可能会导致更严重的大规模基因组重排。在这里,我们综述了关于完成准确 HR 所需的因素和机制的现有知识。