Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair
Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair
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DOI：
10.1016/j.cell.2012.10.021
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发表时间：
2012-11-09
期刊：
影响因子：
64.5
通讯作者：
Jentsch, Stefan
中科院分区：
文献类型：
--
作者：
Psakhye, Ivan;Jentsch, Stefan
SUMO对蛋白质的修饰影响广泛的蛋白质底物。令人惊讶的是，尽管SUMO途径突变体显示出强的表型，但单个SUMO修饰的功能通常是神秘的，并且SUMO化缺陷突变体通常缺乏显著的表型。在这里，我们使用DNA双链断裂修复作为一个例子，并表明，DNA损伤触发SUMO化波，导致同时多位点修饰的几个修复蛋白的相同途径。由DNA结合的SUMO连接酶催化并由单链DNA触发，SUMO化稳定蛋白质之间的物理相互作用。值得注意的是，只有大规模消除几种修复蛋白的SUMO化，才能通过显著减缓DNA修复来显著影响同源重组途径。因此，SUMO协同作用于几种蛋白质，单个修饰只会增加有效的修复。因此，我们认为SUMO化可能经常针对蛋白质组而不是单个蛋白质，而局部修饰酶和高度特异性的触发器确保了特异性。
Protein modification by SUMO affects a wide range of protein substrates. Surprisingly, although SUMO pathway mutants display strong phenotypes, the function of individual SUMO modifications is often enigmatic, and SUMOylation-defective mutants commonly lack notable phenotypes. Here, we use DNA double-strand break repair as an example and show that DNA damage triggers a SUMOylation wave, leading to simultaneous multisite modifications of several repair proteins of the same pathway. Catalyzed by a DNA-bound SUMO ligase and triggered by single-stranded DNA, SUMOylation stabilizes physical interactions between the proteins. Notably, only wholesale elimination of SUMOylation of several repair proteins significantly affects the homologous recombination pathway by considerably slowing down DNA repair. Thus, SUMO acts synergistically on several proteins, and individual modifications only add up to efficient repair. We propose that SUMOylation may thus often target a protein group rather than individual proteins, whereas localized modification enzymes and highly specific triggers ensure specificity.