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

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons79153

Psakhye,  Ivan
Jentsch, Stefan / Molecular Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78165

Jentsch,  Stefan
Jentsch, Stefan / Molecular Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Psakhye, I., & Jentsch, S. (2012). Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair. CELL, 151(4), 807-820. doi:10.1016/j.cell.2012.10.021.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-7A25-3
Abstract
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.