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dc.contributor.authorBermúdez López, Marcelino
dc.contributor.authorVilloria, María Teresa
dc.contributor.authorEsteras, Miguel
dc.contributor.authorJarmuz, Adam
dc.contributor.authorTorres Rosell, Jordi
dc.contributor.authorClemente Blanco, Andrés
dc.contributor.authorAragón, Luis
dc.description.abstractThe 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.ca_ES
dc.description.sponsorshipWe 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).ca_ES
dc.publisherCold Spring Harbor Laboratory Pressca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofGenes & Development, 2016, vol. 30, p. 1339–1356ca_ES
dc.rightscc-by (c) Bermúdez López et al., 2016ca_ES
dc.subjectGenome stabilityca_ES
dc.subjectHomologous recombinationca_ES
dc.subjectSmc complexesca_ES
dc.titleSgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6ca_ES

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cc-by (c) Bermúdez López et al., 2016
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