Laboratory of Hygiene and Public Health, Department of Medical Technology, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara 252-5201, Japan.
Int J Mol Sci. 2022 Jul 25;23(15):8187. doi: 10.3390/ijms23158187.
Cells are constantly exposed to numerous genotoxic stresses that induce DNA damage. DNA double-strand breaks (DSBs) are among the most serious damages and should be systematically repaired to preserve genomic integrity. The efficiency of repair is closely associated with chromatin structure, which is regulated by posttranslational modifications of histones, including ubiquitination. Recent evidence shows crosstalk between histone ubiquitination and DNA damage responses, suggesting an integrated model for the systematic regulation of DNA repair. There are two major pathways for DSB repair, viz., nonhomologous end joining and homologous recombination, and the choice of the pathway is partially controlled by posttranslational modifications of histones, including ubiquitination. Histone ubiquitination changes chromatin structure in the vicinity of DSBs and serves as a platform to select and recruit repair proteins; the removal of these modifications by deubiquitinating enzymes suppresses the recruitment of repair proteins and promotes the convergence of repair reactions. This article provides a comprehensive overview of the DNA damage response regulated by histone ubiquitination in response to DSBs.
细胞不断受到多种致突变应激的影响，这些应激会导致 DNA 损伤。DNA 双链断裂 (DSB) 是最严重的损伤之一，应该进行系统修复以保持基因组完整性。修复的效率与染色质结构密切相关，染色质结构受组蛋白翻译后修饰的调控，包括泛素化。最近的证据表明组蛋白泛素化与 DNA 损伤反应之间存在串扰，这表明 DNA 修复的系统调控存在一个综合模型。DSB 修复有两条主要途径，即非同源末端连接和同源重组，而途径的选择部分受到组蛋白翻译后修饰的控制，包括泛素化。组蛋白泛素化改变 DSB 附近的染色质结构，并作为选择和招募修复蛋白的平台；去泛素化酶去除这些修饰会抑制修复蛋白的募集，并促进修复反应的收敛。本文全面概述了 DSB 引发的组蛋白泛素化对 DNA 损伤反应的调控。
