Relocation of collapsed forks to the nuclear pore complex depends on sumoylation of DNA repair proteins and permits Rad51 association Journal Article

   

Authors:	Whalen, J. M.; Dhingra, N.; Wei, L.; Zhao, X.; Freudenreich, C. H.
Article Title:	Relocation of collapsed forks to the nuclear pore complex depends on sumoylation of DNA repair proteins and permits Rad51 association
Abstract:	Expanded CAG repeats form stem-loop secondary structures that lead to fork stalling and collapse. Previous work has shown that these collapsed forks relocalize to nuclear pore complexes (NPCs) in late S phase in a manner dependent on replication, the nucleoporin Nup84, and the Slx5 protein, which prevents repeat fragility and instability. Here, we show that binding of the Smc5/6 complex to the collapsed fork triggers Mms21-dependent sumoylation of fork-associated DNA repair proteins, and that RPA, Rad52, and Rad59 are the key sumoylation targets that mediate relocation. The SUMO interacting motifs of Slx5 target collapsed forks to the NPC. Notably, Rad51 foci only co-localize with the repeat after it is anchored to the nuclear periphery and Rad51 exclusion from the early collapsed fork is dependent on RPA sumoylation. This pathway may provide a mechanism to constrain recombination at stalled or collapsed forks until it is required for fork restart. © 2020 The Authors Whalen et al. establish the mechanism by which collapsed forks caused by expanded CAG repeats relocate to the nuclear pore complex to maintain genome stability. This mechanism relies on sumoylation of repair proteins that bind the collapsed fork to facilitate relocation and constrain recombination until at the nuclear pore complex. © 2020 The Authors
Keywords:	signal transduction; protein localization; protein motif; dna repair; protein binding; protein interaction; chromosome breakage; dna structure; sumoylation; rad51 protein; replication fork; cag repeat; nuclear pore complex; deoxyribonucleoprotein; trinucleotide repeat; human; priority journal; article; fork collapse; fork relocation; rad52 rad59 sumoylation; rpa sumoylation; smc5-smc6
Journal Title:	Cell Reports
Volume:	31
Issue:	6
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2020-05-12
Start Page:	107635
Language:	English
DOI:	10.1016/j.celrep.2020.107635
PUBMED:	32402281
PROVIDER:	scopus
PMCID:	PMC7344339
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084366669&doi=10.1016%2fj.celrep.2020.107635&partnerID=40&md5=ad24f5911afd64abd04f09676b7496ae
Notes:	Article -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/165901