Nie Minghua, Boddy Michael N
Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Biomolecules. 2016 Feb 25;6(1):14. doi: 10.3390/biom6010014.
Covalent attachment of ubiquitin (Ub) or SUMO to DNA repair proteins plays critical roles in maintaining genome stability. These structurally related polypeptides can be viewed as distinct road signs, with each being read by specific protein interaction motifs. Therefore, via their interactions with selective readers in the proteome, ubiquitin and SUMO can elicit distinct cellular responses, such as directing DNA lesions into different repair pathways. On the other hand, through the action of the SUMO-targeted ubiquitin ligase (STUbL) family proteins, ubiquitin and SUMO can cooperate in the form of a hybrid signal. These mixed SUMO-ubiquitin chains recruit "effector" proteins such as the AAA⁺ ATPase Cdc48/p97-Ufd1-Npl4 complex that contain both ubiquitin and SUMO interaction motifs. This review will summarize recent key findings on collaborative and distinct roles that ubiquitin and SUMO play in orchestrating DNA damage responses.
泛素（Ub）或类泛素化修饰小蛋白（SUMO）与DNA修复蛋白的共价连接在维持基因组稳定性方面起着关键作用。这些结构相关的多肽可被视为不同的路标，每种多肽都由特定的蛋白质相互作用基序识别。因此，通过与蛋白质组中选择性识别蛋白的相互作用，泛素和SUMO可引发不同的细胞反应，如将DNA损伤导向不同的修复途径。另一方面，通过类泛素化修饰小蛋白靶向泛素连接酶（STUbL）家族蛋白的作用，泛素和SUMO可以以混合信号的形式协同作用。这些混合的类泛素化修饰小蛋白 - 泛素链招募“效应器”蛋白，如含有泛素和类泛素化修饰小蛋白相互作用基序的AAA⁺ ATP酶Cdc48/p97 - Ufd1 - Npl4复合物。本综述将总结泛素和类泛素化修饰小蛋白在协调DNA损伤反应中发挥的协同和不同作用的最新关键发现。
