Diverse linkage in polyubiquitin chain structure gives cells an unparalleled complexity to virtually modulate all aspects of cell biology. Substrates can be covalently modified by ubiquitin chains of different topology. Proper DNA damage response takes advantage of this regulatory system and heavily relies on ubiquitin-based signaling. Moreover, increasing evidence suggests that chain specificity dictates DNA repair outcome. In this issue of Genes & Development, Wu and colleagues (pp. 1702-1717) show that Cezanne and Cezanne2, two paralogous deubiquitinating enzymes that are recruited to sites of DNA damage, ensure proper local polyubiquitin chain composition for downstream DNA repair protein assembly. Their study offers a key insight into the mechanism of crosstalk between linkage-specific ubiquitylation at DNA damage sites, while simultaneously raising important questions for future research.

中文翻译：

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混合的泛素链调节DNA修复。

聚泛素链结构中的多样化连接为细胞提供了无与伦比的复杂性，可以虚拟地调节细胞生物学的各个方面。底物可以被具有不同拓扑结构的泛素链共价修饰。适当的DNA损伤反应可利用该调节系统，并严重依赖基于泛素的信号传导。而且，越来越多的证据表明链特异性决定了DNA修复的结果。在本期《基因与发展》中，Wu及其同事（第1702-1717页）显示，塞尚和塞尚2这两种旁源的去泛素化酶被募集到DNA损伤位点，确保下游的DNA修复蛋白组装具有适当的局部多聚泛素链组成。他们的研究提供了对DNA损伤位点的连锁特异性泛素化之间的串扰机制的关键见解，