Caridi P Christopher, Delabaere Laetitia, Zapotoczny Grzegorz, Chiolo Irene
Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA
Philos Trans R Soc Lond B Biol Sci. 2017 Oct 5;372(1731). doi: 10.1098/rstb.2016.0291.
Heterochromatin is mostly composed of repeated DNA sequences prone to aberrant recombination. How cells maintain the stability of these sequences during double-strand break (DSB) repair has been a long-standing mystery. Studies in cells revealed that faithful homologous recombination repair of heterochromatic DSBs relies on the striking relocalization of repair sites to the nuclear periphery before Rad51 recruitment and repair progression. Here, we summarize our current understanding of this response, including the molecular mechanisms involved, and conserved pathways in mammalian cells. We will highlight important similarities with pathways identified in budding yeast for repair of other types of repeated sequences, including rDNA and short telomeres. We will also discuss the emerging role of chromatin composition and regulation in heterochromatin repair progression. Together, these discoveries challenged previous assumptions that repair sites are substantially static in multicellular eukaryotes, that heterochromatin is largely inert in the presence of DSBs, and that silencing and compaction in this domain are obstacles to repair.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'.
异染色质主要由易于发生异常重组的重复DNA序列组成。细胞如何在双链断裂（DSB）修复过程中维持这些序列的稳定性一直是个长期存在的谜团。对细胞的研究表明，异染色质DSB的忠实同源重组修复依赖于在Rad51募集和修复进程之前，修复位点显著重新定位到核周边。在这里，我们总结了目前对这种反应的理解，包括其中涉及的分子机制以及哺乳动物细胞中的保守途径。我们将强调与在芽殖酵母中鉴定出的用于修复其他类型重复序列（包括rDNA和短端粒）的途径的重要相似性。我们还将讨论染色质组成和调控在异染色质修复进程中日益凸显的作用。总之，这些发现挑战了以前的假设，即修复位点在多细胞真核生物中基本是静态的，异染色质在DSB存在时基本是惰性的，以及该区域的沉默和压缩是修复的障碍。本文是主题为“DNA修复和信号传导中的染色质修饰剂和重塑剂”的特刊的一部分。
