The Gurdon Institute, Department of Biochemistry, University of Cambridge, Cambridge CB21QN, United Kingdom.
Genes Dev. 2011 Mar 1;25(5):409-33. doi: 10.1101/gad.2021311.
Genome integrity is constantly monitored by sophisticated cellular networks, collectively termed the DNA damage response (DDR). A common feature of DDR proteins is their mobilization in response to genotoxic stress. Here, we outline how the development of various complementary methodologies has provided valuable insights into the spatiotemporal dynamics of DDR protein assembly/disassembly at sites of DNA strand breaks in eukaryotic cells. Considerable advances have also been made in understanding the underlying molecular mechanisms for these events, with post-translational modifications of DDR factors being shown to play prominent roles in controlling the formation of foci in response to DNA-damaging agents. We review these regulatory mechanisms and discuss their biological significance to the DDR.
基因组完整性由复杂的细胞网络不断监测,这些网络统称为 DNA 损伤反应 (DDR)。DDR 蛋白的一个共同特征是它们在应对遗传毒性应激时的动员。在这里,我们概述了各种互补方法的发展如何为真核细胞中 DNA 链断裂部位 DDR 蛋白组装/拆卸的时空动态提供了有价值的见解。在理解这些事件的潜在分子机制方面也取得了相当大的进展,已经表明 DDR 因子的翻译后修饰在控制对 DNA 损伤剂形成焦点方面发挥着重要作用。我们回顾了这些调节机制,并讨论了它们对 DDR 的生物学意义。