Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6

The RecQ helicase Sgs1 plays critical roles during DNA repair by homologous recombination, fromend resection to Holliday junction (HJ) dissolution. Sgs1 has both pro- and anti-recombinogenic roles, and therefore its activity must be tightly regulated. However, the controls involved in recruitment an...

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Autores: Bermúdez López, Marcelino, Villoria, María Teresa, Esteras, Miguel, Jarmuz, Adam, Torres Rosell, Jordi, Clemente Blanco, Andrés, Aragón, Luis
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/59169
Acceso en línea:https://doi.org/10.1101/gad.278275.116
http://hdl.handle.net/10459.1/59169
Access Level:acceso abierto
Palabra clave:Genome stability
Homologous recombination
Sgs1–Top3
Smc complexes
Smc5/6
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spelling Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6Bermúdez López, MarcelinoVilloria, María TeresaEsteras, MiguelJarmuz, AdamTorres Rosell, JordiClemente Blanco, AndrésAragón, LuisGenome stabilityHomologous recombinationSgs1–Top3Smc complexesSmc5/6The RecQ helicase Sgs1 plays critical roles during DNA repair by homologous recombination, fromend resection to Holliday junction (HJ) dissolution. Sgs1 has both pro- and anti-recombinogenic roles, and therefore its activity must be tightly regulated. However, the controls involved in recruitment and activation of Sgs1 at damaged sites are unknown. Here we show a two-step role for Smc5/6 in recruiting and activating Sgs1 through SUMOylation. First, auto-SUMOylation of Smc5/6 subunits leads to recruitment of Sgs1 as part of the STR (Sgs1–Top3–Rmi1) complex, mediated by two SUMO-interacting motifs (SIMs) on Sgs1 that specifically recognize SUMOylated Smc5/6. Second, Smc5/6-dependent SUMOylation of Sgs1 and Top3 is required for the efficient function of STR. Sgs1 mutants impaired in recognition of SUMOylated Smc5/6 (sgs1-SIMΔ) or SUMO-dead alleles (sgs1-KR) exhibit unprocessed HJs at damaged replication forks, increased crossover frequencies during double-strand break repair, and severe impairment in DNA end resection. Smc5/6 is a key regulator of Sgs1’s recombination functions.We thank the Aragon laboratory for discussions and critical reading of the manuscript.We thank the Clinical Sciences Centre Proteomics Facility (P. Cutillas and P. Faull) for help and advice on our proteomic analysis. Work in J.T.-R.’s laboratory is supported by grants BFU2015-71308-P and BFU2013-50245-EXP from the Spanish Ministry of Economy and Competitivity.Work in the Aragon laboratory was supported by the intramural programme of the Medical Research Council UK and the Wellcome Trust (100955).Cold Spring Harbor Laboratory Press2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1101/gad.278275.116http://hdl.handle.net/10459.1/59169reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)Inglésinfo:eu-repo/grantAgreement/MINECO//BFU2015-71308-Pinfo:eu-repo/grantAgreement/MINECO//BFU2013-50245-EXPReproducció del document publicat a https://doi.org/10.1101/gad.278275.116Genes & Development, 2016, vol. 30, p. 1339–1356cc-by (c) Bermúdez López et al., 2016info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:repositori.udl.cat:10459.1/591692026-06-24T12:42:17Z
dc.title.none.fl_str_mv Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6
title Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6
spellingShingle Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6
Bermúdez López, Marcelino
Genome stability
Homologous recombination
Sgs1–Top3
Smc complexes
Smc5/6
title_short Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6
title_full Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6
title_fullStr Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6
title_full_unstemmed Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6
title_sort Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6
dc.creator.none.fl_str_mv Bermúdez López, Marcelino
Villoria, María Teresa
Esteras, Miguel
Jarmuz, Adam
Torres Rosell, Jordi
Clemente Blanco, Andrés
Aragón, Luis
author Bermúdez López, Marcelino
author_facet Bermúdez López, Marcelino
Villoria, María Teresa
Esteras, Miguel
Jarmuz, Adam
Torres Rosell, Jordi
Clemente Blanco, Andrés
Aragón, Luis
author_role author
author2 Villoria, María Teresa
Esteras, Miguel
Jarmuz, Adam
Torres Rosell, Jordi
Clemente Blanco, Andrés
Aragón, Luis
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Genome stability
Homologous recombination
Sgs1–Top3
Smc complexes
Smc5/6
topic Genome stability
Homologous recombination
Sgs1–Top3
Smc complexes
Smc5/6
description The RecQ helicase Sgs1 plays critical roles during DNA repair by homologous recombination, fromend resection to Holliday junction (HJ) dissolution. Sgs1 has both pro- and anti-recombinogenic roles, and therefore its activity must be tightly regulated. However, the controls involved in recruitment and activation of Sgs1 at damaged sites are unknown. Here we show a two-step role for Smc5/6 in recruiting and activating Sgs1 through SUMOylation. First, auto-SUMOylation of Smc5/6 subunits leads to recruitment of Sgs1 as part of the STR (Sgs1–Top3–Rmi1) complex, mediated by two SUMO-interacting motifs (SIMs) on Sgs1 that specifically recognize SUMOylated Smc5/6. Second, Smc5/6-dependent SUMOylation of Sgs1 and Top3 is required for the efficient function of STR. Sgs1 mutants impaired in recognition of SUMOylated Smc5/6 (sgs1-SIMΔ) or SUMO-dead alleles (sgs1-KR) exhibit unprocessed HJs at damaged replication forks, increased crossover frequencies during double-strand break repair, and severe impairment in DNA end resection. Smc5/6 is a key regulator of Sgs1’s recombination functions.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1101/gad.278275.116
http://hdl.handle.net/10459.1/59169
url https://doi.org/10.1101/gad.278275.116
http://hdl.handle.net/10459.1/59169
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO//BFU2015-71308-P
info:eu-repo/grantAgreement/MINECO//BFU2013-50245-EXP
Reproducció del document publicat a https://doi.org/10.1101/gad.278275.116
Genes & Development, 2016, vol. 30, p. 1339–1356
dc.rights.none.fl_str_mv cc-by (c) Bermúdez López et al., 2016
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv cc-by (c) Bermúdez López et al., 2016
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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