Cell
Volume 151, Issue 4, 9 November 2012, Pages 807-820
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Article
Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair

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Summary

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.

Highlights

► DNA damage induces a SUMOylation wave targeting multiple DSB repair proteins ► The SUMOylation wave is triggered by a DNA-bound ligase and resected ssDNA ► Protein group SUMOylation fosters DSB repair protein association ► Protein group SUMOylation of DSB repair proteins accelerates repair

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