DNA repair and global sumoylation are regulated by distinct Ubc9 noncovalent complexes |
| |
| Authors: | Prudden John Perry J Jefferson P Nie Minghua Vashisht Ajay A Arvai Andrew S Hitomi Chiharu Guenther Grant Wohlschlegel James A Tainer John A Boddy Michael N |
| |
| Institution: | 1Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037;2School of Biotechnology, Amrita University, Kollam, Kerala 690525, India;3Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, California 90095;4Life Sciences Division, Department of Molecular Biology, Lawrence Berkeley National Laboratory, Berkeley, California |
| |
| 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. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
|
