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

J Prudden, JJP Perry, M Nie, AA Vashisht… - … and cellular biology, 2011 - Taylor & Francis
J Prudden, JJP Perry, M Nie, AA Vashisht, AS Arvai, C Hitomi, G Guenther, JA Wohlschlegel
Molecular and cellular biology, 2011Taylor & Francis
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 …
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.
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