Department of Biochemistry and Molecular Pharmacology.
Perlmutter Cancer Center.
Genes Dev. 2019 Dec 1;33(23-24):1615-1616. doi: 10.1101/gad.334383.119.
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 , 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.
多聚泛素链结构中的多样性连接赋予了细胞无与伦比的复杂性，几乎可以调节细胞生物学的各个方面。底物可以通过不同拓扑结构的泛素链共价修饰。适当的 DNA 损伤反应利用了这个调节系统，并严重依赖于基于泛素的信号转导。此外，越来越多的证据表明，链特异性决定了 DNA 修复的结果。在本期的《细胞》杂志中，Wu 及其同事（第 1702-1717 页）表明，两个在 DNA 损伤部位被招募的具有平行功能的去泛素化酶 Cezanne 和 Cezanne2，可确保适当的局部多泛素链组成，从而进行下游 DNA 修复蛋白的组装。他们的研究为 DNA 损伤部位特异性连接泛素化的串扰机制提供了一个关键的见解，同时也为未来的研究提出了一些重要的问题。
