Ubiquitin Signaling Group, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Nat Rev Mol Cell Biol. 2016 May 23;17(6):379-94. doi: 10.1038/nrm.2016.58.
DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions. The swift recognition and faithful repair of such damage is crucial for the maintenance of genomic stability, as well as for cell and organismal fitness. Signalling by ubiquitin, SUMO and other ubiquitin-like modifiers (UBLs) orchestrates and regulates cellular responses to DSBs at multiple levels, often involving extensive crosstalk between these modifications. Recent findings have revealed compelling insights into the complex mechanisms by which ubiquitin and UBLs regulate protein interactions with DSB sites to promote accurate lesion repair and protection of genome integrity in mammalian cells. These advances offer new therapeutic opportunities for diseases linked to genetic instability.
DNA 双链断裂 (DSBs) 是一种具有高细胞毒性的 DNA 损伤。迅速识别和准确修复此类损伤对于维持基因组稳定性以及细胞和生物体的适应性至关重要。泛素、SUMO 和其他泛素样修饰物 (UBLs) 的信号转导在多个层面上协调和调节细胞对 DSB 的反应，通常涉及这些修饰之间的广泛串扰。最近的发现揭示了令人信服的见解，即泛素和 UBL 如何调节与 DSB 位点结合的蛋白质相互作用，以促进哺乳动物细胞中损伤的准确修复和基因组完整性的保护。这些进展为与遗传不稳定性相关的疾病提供了新的治疗机会。
