3goe
Molecular Mimicry of SUMO promotes DNA repair
Structural highlights
FunctionRAD60_SCHPO Required for repair of DNA double strand breaks which occur during replication, or induced by UV or gamma radiation, via recombination between sister chromatids. This has a subsequent role in the maintenance of chromosome structure. May work in conjunction with the Smc5-Smc6 complex.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedRad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). We show here that despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. The molecular basis of this selectivity is revealed by our 0.97-A resolution crystal structure of Rad60 SLD2, which shows that apart from the conserved non-substrate SUMO:Ubc9 interface, the surface features of SLD2 are distinct from those of SUMO. Abrogation of the SLD2:Ubc9 FEG motif-dependent interaction results in hypersensitivity to genotoxic stress and an increase in spontaneous recombination associated with aberrant replication forks. Our results provide a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating sumoylation. Molecular mimicry of SUMO promotes DNA repair.,Prudden J, Perry JJ, Arvai AS, Tainer JA, Boddy MN Nat Struct Mol Biol. 2009 May;16(5):509-16. Epub 2009 Apr 12. PMID:19363481[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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