Chen Zulong, Tyler Jessica K
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York City, NY, United States.
Front Cell Dev Biol. 2022 Jun 8;10:909696. doi: 10.3389/fcell.2022.909696. eCollection 2022.
DNA double-strand breaks (DSBs), the most deleterious DNA lesions, are primarily repaired by two pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ), the choice of which is largely dependent on cell cycle phase and the local chromatin landscape. Recent studies have revealed that post-translational modifications on histones play pivotal roles in regulating DSB repair pathways including repair pathway choice. In this review, we present our current understanding of how these DSB repair pathways are employed in various chromatin landscapes to safeguard genomic integrity. We place an emphasis on the impact of different histone post-translational modifications, characteristic of euchromatin or heterochromatin regions, on DSB repair pathway choice. We discuss the potential roles of damage-induced chromatin modifications in the maintenance of genome and epigenome integrity. Finally, we discuss how RNA transcripts from the vicinity of DSBs at actively transcribed regions also regulate DSB repair pathway choice.
DNA双链断裂（DSB）是最有害的DNA损伤，主要通过两条途径修复，即同源重组（HR）和非同源末端连接（NHEJ），其选择很大程度上取决于细胞周期阶段和局部染色质景观。最近的研究表明，组蛋白的翻译后修饰在调节包括修复途径选择在内的DSB修复途径中起关键作用。在这篇综述中，我们阐述了目前对于这些DSB修复途径如何在各种染色质景观中被用于维护基因组完整性的理解。我们重点关注常染色质或异染色质区域特有的不同组蛋白翻译后修饰对DSB修复途径选择的影响。我们讨论了损伤诱导的染色质修饰在维持基因组和表观基因组完整性中的潜在作用。最后，我们讨论了来自活跃转录区域DSB附近的RNA转录本如何也调节DSB修复途径的选择。
