Meiotic Double-Strand Break Proteins Influence Repair Pathway Utilization
Meiotic Double-Strand Break Proteins Influence Repair Pathway Utilization
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DOI：
10.1534/genetics.118.301402
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发表时间：
2018-11-01
期刊：
影响因子：
3.3
通讯作者：
Yanowitz, Judith L.
中科院分区：
文献类型：
--
作者：
Macaisne, Nicolas;Kessler, Zebulin;Yanowitz, Judith L.
双链断裂（DSB）是DNA所能承受的最有害的损伤之一。然而，DSB在减数分裂开始时被编程，并且需要促进子细胞中倍性的适当降低。这些断裂的修复受到严格控制，以有利于同源重组（HR），这是唯一可以形成交叉的修复途径。然而，很少有人知道替代修复途径的活动是如何在这些阶段进行调节。我们发现了一个意想不到的合成之间的相互作用的DSB机制和链交换蛋白质。耗尽秀丽隐杆线虫DSB促进因子HIM-5和DSB-2抑制了在缺乏RAD-51或其他链交换介质的情况下出现的染色体融合的形成。我们的研究表明，非同源和θ介导的末端连接（c-NHEJ和TMEJ，分别）和单链退火（SSA）冗余功能修复DSB时，HR受到损害，HIM-5影响TMEJ和SSA的利用。
Double-strand breaks (DSBs) are among the most deleterious lesions DNA can endure. Yet, DSBs are programmed at the onset of meiosis, and are required to facilitate appropriate reduction of ploidy in daughter cells. Repair of these breaks is tightly controlled to favor homologous recombination (HR)the only repair pathway that can form crossovers. However, little is known about how the activities of alternative repair pathways are regulated at these stages. We discovered an unexpected synthetic interaction between the DSB machinery and strand-exchange proteins. Depleting the Caenorhabditis elegans DSB-promoting factors HIM-5 and DSB-2 suppresses the formation of chromosome fusions that arise in the absence of RAD-51 or other strand-exchange mediators. Our investigations reveal that nonhomologous and theta-mediated end joining (c-NHEJ and TMEJ, respectively) and single strand annealing (SSA) function redundantly to repair DSBs when HR is compromised, and that HIM-5 influences the utilization of TMEJ and SSA.