Department of Genetics, Medical Genetics Center, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Epigenetics Chromatin. 2012 Jan 30;5:4. doi: 10.1186/1756-8935-5-4.
The integrity of DNA is continuously challenged by metabolism-derived and environmental genotoxic agents that cause a variety of DNA lesions, including base alterations and breaks. DNA damage interferes with vital processes such as transcription and replication, and if not repaired properly, can ultimately lead to premature aging and cancer. Multiple DNA pathways signaling for DNA repair and DNA damage collectively safeguard the integrity of DNA. Chromatin plays a pivotal role in regulating DNA-associated processes, and is itself subject to regulation by the DNA-damage response. Chromatin influences access to DNA, and often serves as a docking or signaling site for repair and signaling proteins. Its structure can be adapted by post-translational histone modifications and nucleosome remodeling, catalyzed by the activity of ATP-dependent chromatin-remodeling complexes. In recent years, accumulating evidence has suggested that ATP-dependent chromatin-remodeling complexes play important, although poorly characterized, roles in facilitating the effectiveness of the DNA-damage response. In this review, we summarize the current knowledge on the involvement of ATP-dependent chromatin remodeling in three major DNA repair pathways: nucleotide excision repair, homologous recombination, and non-homologous end-joining. This shows that a surprisingly large number of different remodeling complexes display pleiotropic functions during different stages of the DNA-damage response. Moreover, several complexes seem to have multiple functions, and are implicated in various mechanistically distinct repair pathways.
DNA 的完整性不断受到代谢衍生和环境遗传毒性物质的挑战，这些物质会导致各种 DNA 损伤，包括碱基改变和断裂。DNA 损伤会干扰转录和复制等重要过程，如果不能正确修复，最终可能导致过早衰老和癌症。多种参与 DNA 修复和 DNA 损伤信号转导的 DNA 通路共同保护 DNA 的完整性。染色质在调节与 DNA 相关的过程中起着关键作用，其本身也受到 DNA 损伤反应的调节。染色质影响 DNA 的可及性，并且通常作为修复和信号蛋白的对接或信号位点。其结构可以通过翻译后组蛋白修饰和核小体重塑来适应，这是由 ATP 依赖性染色质重塑复合物的活性催化的。近年来，越来越多的证据表明，ATP 依赖性染色质重塑复合物在促进 DNA 损伤反应的有效性方面发挥着重要作用，尽管其作用机制尚未完全阐明。在这篇综述中，我们总结了目前关于 ATP 依赖性染色质重塑在三种主要 DNA 修复途径中的参与情况：核苷酸切除修复、同源重组和非同源末端连接。这表明，在 DNA 损伤反应的不同阶段，数量惊人的不同重塑复合物表现出多效性功能。此外，一些复合物似乎具有多种功能，并与各种机制上不同的修复途径有关。
