Dantuma Nico P, Pfeiffer Annika
Department of Cell and Molecular Biology, Karolinska Institutet Stockholm, Sweden.
Front Genet. 2016 Apr 11;7:58. doi: 10.3389/fgene.2016.00058. eCollection 2016.
Ubiquitin and the ubiquitin-like modifier SUMO are intimately connected with the cellular response to various types of DNA damage. A striking feature is the local accumulation of these proteinaceous post-translational modifications in the direct vicinity to DNA double-strand breaks, which plays a critical role in the formation of ionizing radiation-induced foci. The functional significance of these modifications is the coordinated recruitment and removal of proteins involved in DNA damage signaling and repair in a timely manner. The central orchestrators of these processes are the ubiquitin and SUMO ligases that are responsible for accurately tagging a broad array of chromatin and chromatin-associated proteins thereby changing their behavior or destination. Despite many differences in the mode of action of these enzymes, they share some striking features that are of direct relevance for their function in the DNA damage response. In this review, we outline the molecular mechanisms that are responsible for the recruitment of ubiquitin and SUMO ligases and discuss the importance of chromatin proximity in this process.
泛素和类泛素修饰因子SUMO与细胞对各种类型DNA损伤的反应密切相关。一个显著特征是这些蛋白质翻译后修饰在DNA双链断裂的紧邻区域局部积累，这在电离辐射诱导灶的形成中起关键作用。这些修饰的功能意义在于及时协调招募和去除参与DNA损伤信号传导和修复的蛋白质。这些过程的核心协调者是泛素和SUMO连接酶，它们负责精确标记大量染色质和染色质相关蛋白，从而改变它们的行为或去向。尽管这些酶的作用方式存在许多差异，但它们具有一些与其在DNA损伤反应中的功能直接相关的显著特征。在本综述中，我们概述了负责招募泛素和SUMO连接酶的分子机制，并讨论了染色质接近度在这一过程中的重要性。
