Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
DNA Repair (Amst). 2021 Jul;103:103129. doi: 10.1016/j.dnarep.2021.103129. Epub 2021 May 7.
Genome integrity is constantly challenged by various DNA lesions with DNA double-strand breaks (DSBs) as the most cytotoxic lesions. In order to faithfully repair DSBs, DNA damage response (DDR) signaling networks have evolved, which organize many multi-protein complexes to deal with the encountered DNA damage. Spatiotemporal dynamics of these protein complexes at DSBs are mainly modulated by post-translational modifications (PTMs). One of the most well-studied PTMs in DDR is ubiquitylation which can orchestrate cellular responses to DSBs, promote accurate DNA repair, and maintain genome integrity. Here, we summarize the recent advances of ubiquitin-dependent signaling in DDR and discuss how ubiquitylation crosstalks with other PTMs to control fundamental biological processes in DSB repair.
基因组完整性不断受到各种 DNA 损伤的挑战,其中 DNA 双链断裂 (DSB) 是最具细胞毒性的损伤。为了忠实地修复 DSB,已经进化出 DNA 损伤反应 (DDR) 信号网络,该网络组织了许多多蛋白复合物来处理遇到的 DNA 损伤。这些蛋白质复合物在 DSB 处的时空动态主要由翻译后修饰 (PTM) 调节。DDR 中研究最多的 PTM 之一是泛素化,它可以协调细胞对 DSB 的反应,促进 DNA 修复的准确性,并维持基因组的完整性。在这里,我们总结了 DDR 中泛素依赖性信号的最新进展,并讨论了泛素化如何与其他 PTM 相互作用来控制 DSB 修复中的基本生物学过程。