title: DNA repair and global sumoylation are regulated by distinct Ubc9 noncovalent complexes.
abstract: Global sumoylation, SUMO chain formation, and genome stabilization are all outputs generated by a limited repertoire of enzymes. Mechanisms driving selectivity for each of these processes are largely uncharacterized. Here, through crystallographic analyses we show that the SUMO E2 Ubc9 forms a noncovalent complex with a SUMO-like domain of Rad60 (SLD2). Ubc9:SLD2 and Ubc9:SUMO noncovalent complexes are structurally analogous, suggesting that differential recruitment of Ubc9 by SUMO or Rad60 provides a novel means for such selectivity. Indeed, deconvoluting Ubc9 function by disrupting either the Ubc9:SLD2 or Ubc9:SUMO noncovalent complex reveals distinct roles in facilitating sumoylation. Ubc9:SLD2 acts in the Nse2 SUMO E3 ligase-dependent pathway for DNA repair, whereas Ubc9:SUMO instead promotes global sumoylation and chain formation, via the Pli1 E3 SUMO ligase. Moreover, this Pli1-dependent SUMO chain formation causes the genome instability phenotypes of SUMO-targeted ubiquitin ligase (STUbL) mutants. Overall, we determine that, unexpectedly, Ubc9 noncovalent partner choice dictates the role of sumoylation in distinct cellular pathways.
authors: Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors: John
authors: J
authors: Prudden
authors: J Jefferson P
authors: JJ
authors: Perry
authors: Minghua
authors: M
authors: Nie
authors: Ajay A
authors: AA
authors: Vashisht
authors: Andrew S
authors: AS
authors: Arvai
authors: Chiharu
authors: C
authors: Hitomi
authors: Grant
authors: G
authors: Guenther
authors: James A
authors: JA
authors: Wohlschlegel
authors: John A
authors: JA
authors: Tainer
authors: Michael N
authors: MN
authors: Boddy
mesh_terms: D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004260:DNA Repair; D006801:Humans; D013058:Mass Spectrometry; D008958:Models, Molecular; D009154:Mutation; D020836:Protein Structure, Quaternary; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D058207:Sumoylation; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; C559642:NFATC2IP protein, human; C479823:Nse2 protein, S pombe; C455501:Rad60 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9