School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520.
Mutat Res Rev Mutat Res. 2019 Apr-Jun;780:29-36. doi: 10.1016/j.mrrev.2017.10.002. Epub 2017 Nov 7.
Chromatin is a significant barrier to many DNA damage response (DDR) factors, such as DNA repair enzymes, that process DNA lesions to reduce mutations and prevent cell death; yet, paradoxically, chromatin also has a critical role in many signaling pathways that regulate the DDR. The primary level of DNA packaging in chromatin is the nucleosome core particle (NCP), consisting of DNA wrapped around an octamer of the core histones H2A, H2B, H3 and H4. Here, we review recent studies characterizing how the packaging of DNA into nucleosomes modulates the activity of the base excision repair (BER) pathway and dictates BER subpathway choice. We also review new evidence indicating that the histone amino-terminal tails coordinately regulate multiple DDR pathways during the repair of alkylation damage in the budding yeast
染色质是许多 DNA 损伤反应 (DDR) 因子的重要障碍,如修复酶,这些酶处理 DNA 损伤以减少突变并防止细胞死亡;然而,矛盾的是,染色质在许多调节 DDR 的信号通路中也起着关键作用。染色质中 DNA 包装的主要层次是核小体核心颗粒 (NCP),由 DNA 缠绕在核心组蛋白 H2A、H2B、H3 和 H4 的八聚体上组成。在这里,我们回顾了最近的研究,这些研究描述了 DNA 包装成核小体如何调节碱基切除修复 (BER) 途径的活性,并决定了 BER 亚途径的选择。我们还回顾了新的证据,表明组蛋白氨基末端尾巴在修复芽殖酵母中的烷化损伤时协调调节多种 DDR 途径。