title: Small ubiquitin-like modifier (SUMO) isoforms and conjugation-independent function in DNA double-strand break repair pathways.
abstract: Small ubiquitin-like modifier (SUMO) proteins act in DNA double-strand break (DSB) repair, but the pathway specificity of the three major isoforms has not been defined. In experiments in which we depleted the endogenous SUMO protein by RNAi, we found that SUMO1 functioned in all subpathways of either homologous recombination (HR) or non-homologous end joining (NHEJ), whereas SUMO2/3 was required for the major NHEJ pathway, called conservative NHEJ, but dispensable in other DSB repair pathways. To our surprise, we found that depletion of UBC9, the unique SUMO E2 enzyme, had no effect in HR or alternative NHEJ (Alt-NHEJ) but was required for conservative NHEJ. Consistent with this result, both non-conjugatable mutant and wild-type SUMO1 proteins functioned similarly in HR and Alt-NHEJ. These results detail the functional roles of specific SUMO isoforms in DSB repair in mammalian cells and reveal that SUMO1 functions in HR or Alt-NHEJ as a free protein and not as a protein conjugate.
authors: From the Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio 43210.
authors: Yiheng
authors: Y
authors: Hu
authors: From the Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio 43210 Jeffrey.Parvin@osumc.edu.
authors: Jeffrey D
authors: JD
authors: Parvin
mesh_terms: D001483:Base Sequence; D004249:DNA Damage; D004260:DNA Repair; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; D034741:RNA, Small Interfering; D025841:Small Ubiquitin-Related Modifier Proteins
keywords: DNA Damage Response; Double-strand Break Repair; Homologous Recombination; Non-homologous End Joining; SUMO-interacting Motif (SIM); Small Ubiquitin-like Modifier (SUMO); Sumoylation; UBC9