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Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair

zhangxia111 添加于 2012/11/5 16:52:45  28269次阅读 | 0次推荐 | 257个评论

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.

作 者:Ivan Psakhye, Stefan Jentsch
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学科领域:生命科学 » 遗传学与生物信息学 » 基因表达调控与表观遗传学
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原文链接:http://www.cell.com/abstract/S0092-8674(12)01241-X
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