DNA repair and global sumoylation are regulated by distinct Ubc9 noncovalent complexes

Mol Cell Biol. 2011 Jun;31(11):2299-310. doi: 10.1128/MCB.05188-11. Epub 2011 Mar 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Blotting, Western
  • Carrier Proteins / chemistry
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Crystallography, X-Ray
  • DNA Repair*
  • Humans
  • Mass Spectrometry
  • Models, Molecular
  • Mutation
  • Protein Structure, Quaternary
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Small Ubiquitin-Related Modifier Proteins / biosynthesis
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Sumoylation
  • Ubiquitin-Conjugating Enzymes / chemistry
  • Ubiquitin-Conjugating Enzymes / metabolism*

Substances

  • Carrier Proteins
  • Chromosomal Proteins, Non-Histone
  • NFATC2IP protein, human
  • Nse2 protein, S pombe
  • Rad60 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Ubiquitin-Conjugating Enzymes
  • ubiquitin-conjugating enzyme UBC9

Associated data

  • PDB/3RCZ
  • PDB/3RD2