Epigenetics and Genome Stability Team, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.
ISREC Foundation, and University of Lausanne, Agora Cancer Research Center, Rue du Bugnon 25a, 1005 Lausanne, Switzerland.
Curr Opin Cell Biol. 2024 Oct;90:102405. doi: 10.1016/j.ceb.2024.102405. Epub 2024 Jul 30.
The substrate for the repair of DNA damage in living cells is not DNA but chromatin. Chromatin bears a range of modifications, which in turn bind ligands that compact or open chromatin structure, and determine its spatial organization within the nucleus. In some cases, RNA in the form of RNA:DNA hybrids or R-loops modulates DNA accessibility. Each of these parameters can favor particular pathways of repair. Chromatin or nucleosome remodelers are key regulators of chromatin structure, and a number of remodeling complexes are implicated in DNA repair. We cover novel insights into the impact of chromatin structure, nuclear organization, R-loop formation, nuclear actin, and nucleosome remodelers in DNA double-strand break repair, focusing on factors that alter repair functional upon ablation.
活细胞中 DNA 损伤修复的底物不是 DNA,而是染色质。染色质带有一系列修饰,这些修饰反过来结合配体,使染色质结构紧缩或展开,并决定其在核内的空间组织。在某些情况下,以 RNA:DNA 杂交体或 R 环形式存在的 RNA 调节 DNA 的可及性。这些参数中的每一个都可以有利于特定的修复途径。染色质或核小体重塑因子是染色质结构的关键调节剂,许多重塑复合物都与 DNA 修复有关。我们介绍了关于染色质结构、核组织、R 环形成、核肌动蛋白和核小体重塑因子对 DNA 双链断裂修复的影响的新见解,重点介绍了在消融后改变修复功能的因素。