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dc.contributor.authorZapatka, Mariel
dc.contributor.authorPociño Merino, Irene
dc.contributor.authorHeluani-Gahete, Hayat
dc.contributor.authorBermúdez López, Marcelino
dc.contributor.authorTarrés, Marc
dc.contributor.authorIbars Estiarte, Eva Irene
dc.contributor.authorSolé-Soler, Roger
dc.contributor.authorGutiérrez-Escribano, Pilar
dc.contributor.authorApostolova, Sonia
dc.contributor.authorCasas Herranz, Celia
dc.contributor.authorAragon, Luis
dc.contributor.authorWellinger, Ralf Erik
dc.contributor.authorColomina i Gabarrella, Neus
dc.contributor.authorTorres Rosell, Jordi
dc.description.abstractReplication of a damaged DNA template can threaten the integrity of the genome, requiring the use of various mechanisms to tolerate DNA lesions. The Smc5/6 complex, together with the Nse2/Mms21 SUMO ligase, plays essential roles in genome stability through undefined tasks at damaged replication forks. Various subunits within the Smc5/6 complex are substrates of Nse2, but we currently do not know the role of these modifications. Here we show that sumoylation of Smc5 is targeted to its coiled-coil domain, is upregulated by replication fork damage, and participates in bypass of DNA lesions. smc5-KR mutant cells display defects in formation of sister chromatid junctions and higher translesion synthesis. Also, we provide evidence indicating that Smc5 sumoylation modulates Mph1-dependent fork regression, acting synergistically with other pathways to promote chromosome disjunction. We propose that sumoylation of Smc5 enhances physical remodeling of damaged forks, avoiding the use of a more mutagenic tolerance pathway.ca_ES
dc.description.sponsorshipWork in the J.T.-R. lab was supported by grants BFU2015-71308-P and PGC2018-097796-B-I00 from Ministerio de Ciencia, Innovación y Universidades and grant 2017-SGR-569 from AGAUR-Generalitat de Catalunya ; the IRBLLEIDA Institute is part of CERCA Programme/Generalitat de Catalunya. R.W. was funded by grant BFU2015-69183-P . Work in the L.A. laboratory was supported by a Wellcome Trust Senior Investigator Award to L.A. ( 100955 , “Functional Dissection of Mitotic Chromatin”) and the London Institute of Medical Research (LMS), which receives its core funding from the UK Medical Research Council. We thank Laia de Nadal for the BY5563 yeast strain, Jim Haber for the BIR strain, Boris Pfander for the slx4-S486A mutant, and Patrick Sung for kindly sharing materials and helpful advice; Sònia Rius, Seba Almedawar, and Clàudia Guasch for construction of yeast strains and smc5-KR plasmids; Hélène Gaillard for analysis and statistical analysis of 2D gel intermediates; Carolina de la Torre for the proteomic analysis of Smc5-SUMO peptides; and Andrés Clemente, Jose Antonio Tercero, and all members of the Cell Cycle lab for helpful discussions.ca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofCell Reports, 2019, vol. 29, núm. 10, p. 3160-3172ca_ES
dc.rightscc-by, (c) Zapatka et al., 2019ca_ES
dc.subjectDNA damage toleranceca_ES
dc.subjectFork regressionca_ES
dc.subjectDNA replicationca_ES
dc.titleSumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forksca_ES

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