Alternative end-joining pathway(s): Bricolage at DNA breaks
Alternative end-joining pathway(s): Bricolage at DNA breaks
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DOI：
10.1016/j.dnarep.2014.02.007
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发表时间：
2014-05-01
期刊：
影响因子：
3.8
通讯作者：
Calsou, Patrick
中科院分区：
文献类型：
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作者：
Frit, Philippe;Barboule, Nadia;Calsou, Patrick
为了科普DNA双链断裂（DSB）的遗传毒性，细胞已经进化出两种主要的修复途径：使用同源DNA序列作为修复模板的同源重组，以及涉及通过DNA连接酶IV（Lig 4）直接密封DSB末端的非同源Ku依赖性末端连接。在过去的二十年中，出现了第三个参与者，最常被称为替代性末端连接（A-EJ），其被定义为任何Ku或Lig 4独立的末端连接过程。A-EJ越来越多地出现在DSB上作为一个高度易错的拼凑，尽管不断扩大的探索，它仍然逃脱了充分的表征。本文就A-EJ的调控机制及其在生理和病理条件下的生物学意义进行综述，并着重讨论了A-EJ与染色体不稳定性和癌症的关系。无论它是否是一个真正的DSB修复途径，A-EJ正在成为一个重要的细胞过程，了解A-EJ肯定会是未来几年的一个重大挑战。(C)2014作者由爱思唯尔公司出版
To cope with DNA double strand break (DSB) genotoxicity, cells have evolved two main repair pathways: homologous recombination which uses homologous DNA sequences as repair templates, and non-homologous Ku-dependent end-joining involving direct sealing of DSB ends by DNA ligase IV (Lig4). During the last two decades a third player most commonly named alternative end-joining (A-EJ) has emerged, which is defined as any Ku- or Lig4-independent end-joining process. A-EJ increasingly appears as a highly error-prone bricolage on DSBs and despite expanding exploration, it still escapes full characterization. In the present review, we discuss the mechanism and regulation of A-EJ as well as its biological relevance under physiological and pathological situations, with a particular emphasis on chromosomal instability and cancer. Whether or not it is a genuine DSB repair pathway, A-EJ is emerging as an important cellular process and understanding A-EJ will certainly be a major challenge for the coming years. (C) 2014 The Authors. Published by Elsevier B.V.