Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Cold Spring Harb Perspect Biol. 2013 May 1;5(5):a012757. doi: 10.1101/cshperspect.a012757.
Nonhomologous end joining (NHEJ) refers to a set of genome maintenance pathways in which two DNA double-strand break (DSB) ends are (re)joined by apposition, processing, and ligation without the use of extended homology to guide repair. Canonical NHEJ (c-NHEJ) is a well-defined pathway with clear roles in protecting the integrity of chromosomes when DSBs arise. Recent advances have revealed much about the identity, structure, and function of c-NHEJ proteins, but many questions exist regarding their concerted action in the context of chromatin. Alternative NHEJ (alt-NHEJ) refers to more recently described mechanism(s) that repair DSBs in less-efficient backup reactions. There is great interest in defining alt-NHEJ more precisely, including its regulation relative to c-NHEJ, in light of evidence that alt-NHEJ can execute chromosome rearrangements. Progress toward these goals is reviewed.
非同源末端连接(NHEJ)是指一组基因组维护途径,其中两个 DNA 双链断裂(DSB)末端通过贴合、加工和连接而重新连接,而不使用扩展同源性来指导修复。规范的 NHEJ(c-NHEJ)是一条明确的途径,当 DSB 出现时,它在保护染色体完整性方面发挥着明确的作用。最近的进展揭示了 c-NHEJ 蛋白的身份、结构和功能,但在染色质背景下它们协同作用的许多问题仍然存在。替代 NHEJ(alt-NHEJ)是指最近描述的一种机制,它以较低效率的备份反应修复 DSB。鉴于 alt-NHEJ 可以执行染色体重排的证据,人们非常有兴趣更精确地定义 alt-NHEJ,包括其相对于 c-NHEJ 的调节,这方面的进展正在被审查。