DNA double-strand breaks (DSBs) are one of the most dangerous assaults on the genome, and yet their natural and programmed production are inherent to life. When DSBs arise close together they are particularly deleterious, and their repair may require an altered form of the DNA damage response. Our understanding of how clustered DSBs are repaired in the germline is unknown. Using laser microirradiation, we examine early events in the repair of clustered DSBs in germ cells within Caenorhabditis elegans. We use precise temporal resolution to show how the recruitment of MRE-11 to complex damage is regulated, and that clustered DNA damage can recruit proteins from various repair pathways. Abrogation of non-homologous end joining or COM-1 attenuates the recruitment of MRE-11 through distinct mechanisms. The synaptonemal complex plays both positive and negative regulatory roles in these mutant contexts. These findings indicate that MRE-11 is regulated by modifying its accessibility to chromosomes.

DNA 双链断裂 (DSB) 是对基因组最危险的攻击之一，但它们的自然和程序化生产是生命固有的。当 DSB 紧密结合在一起时，它们尤其有害，它们的修复可能需要改变 DNA 损伤反应的形式。我们对如何在生殖系中修复聚集的 DSB 的理解尚不清楚。使用激光微辐照，我们检查了秀丽隐杆线虫生殖细胞中簇状 DSB 修复的早期事件. 我们使用精确的时间分辨率来显示如何调节 MRE-11 对复杂损伤的募集，以及聚集的 DNA 损伤可以从各种修复途径中募集蛋白质。取消非同源末端连接或 COM-1 通过不同的机制减弱了 MRE-11 的募集。联会复合体在这些突变环境中起着积极和消极的调节作用。这些发现表明，MRE-11 是通过改变其对染色体的可及性来调节的。