Esc2 orchestrates substrate-specific sumoylation by acting as a SUMO E2 cofactor in genome maintenance Journal Article


Authors: Li, S.; Bonner, J. N.; Wan, B.; So, S.; Summers, A.; Gonzalez, L.; Xue, X.; Zhao, X.
Article Title: Esc2 orchestrates substrate-specific sumoylation by acting as a SUMO E2 cofactor in genome maintenance
Abstract: SUMO modification regulates diverse cellular processes by targeting hundreds of proteins. However, the limited number of sumoylation enzymes raises the question of how such a large number of substrates are efficiently modified. Specifically, how genome maintenance factors are dynamically sumoylated at DNA replication and repair sites to modulate their functions is poorly understood. Here, we demonstrate a role for the conserved yeast Esc2 protein in this process by acting as a SUMO E2 cofactor. Esc2 is required for genome stability and binds to Holliday junctions and replication fork structures. Our targeted screen found that Esc2 promotes the sumoylation of a Holliday junction dissolution complex and specific replisome proteins. Esc2 does not elicit these effects via stable interactions with substrates or their common SUMO E3. Rather, we show that a SUMO-like domain of Esc2 stimulates sumoylation by exploiting a noncovalent SUMO binding site on the E2 enzyme. This role of Esc2 in sumoylation is required for Holliday junction clearance and genome stability. Our findings thus suggest that Esc2 acts as a SUMO E2 cofactor at distinct DNA structures to promote the sumoylation of specific substrates and genome maintenance. © 2021 Li et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
Keywords: homologous recombination; genome maintenance; esc2; sumo e2
Journal Title: Genes and Development
Volume: 35
Issue: 3-4
ISSN: 0890-9369
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2021-02-01
Start Page: 261
End Page: 272
Language: English
DOI: 10.1101/gad.344739.120
PUBMED: 33446573
PROVIDER: scopus
PMCID: PMC7849368
DOI/URL:
Notes: Article -- Export Date: 1 April 2021 -- Source: Scopus
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  1. Xiaolan Zhao
    77 Zhao
  2. Bingbing   Wan
    6 Wan
  3. Shibai Li
    10 Li