Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks

Replication 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 fork...

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Autores: Zapatka, Mariel, Pociño Merino, Irene, Heluani-Gahete, Hayat, Bermúdez López, Marcelino, Tarrés Escalona, Marc, Ibars Estiarte, Eva Irene, Solé-Soler, Roger, Gutiérrez-Escribano, Pilar, Apostolova, Sonia, Casas Herranz, Celia, Aragon, Luis, Wellinger, Ralf Erik, Colomina i Gabarrella, Neus, Torres Rosell, Jordi
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2019
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/68304
Acesso em linha:https://doi.org/10.1016/j.celrep.2019.10.123
http://hdl.handle.net/10459.1/68304
Access Level:Acceso aberto
Palavra-chave:Smc5
Nse2
Mms21
SUMO
Mph1
DNA damage tolerance
Fork regression
DNA replication
Yeast
Chromosome
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spelling Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication ForksZapatka, MarielPociño Merino, IreneHeluani-Gahete, HayatBermúdez López, MarcelinoTarrés Escalona, MarcIbars Estiarte, Eva IreneSolé-Soler, RogerGutiérrez-Escribano, PilarApostolova, SoniaCasas Herranz, CeliaAragon, LuisWellinger, Ralf ErikColomina i Gabarrella, NeusTorres Rosell, JordiSmc5Nse2Mms21SUMOMph1DNA damage toleranceFork regressionDNA replicationYeastChromosomeReplication 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.Work 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.Elsevier202020202019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1016/j.celrep.2019.10.123http://hdl.handle.net/10459.1/68304http://hdl.handle.net/10459.1/68304reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/grantAgreement/MINECO//BFU2015-71308-Pinfo:eu-repo/grantAgreement/MINECO//BFU2015-69183-Pinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-097796-B-I00Reproducció del document publicat a https://doi.org/10.1016/j.celrep.2019.10.123Cell Reports, 2019, vol. 29, núm. 10, p. 3160-3172cc-by, (c) Zapatka et al., 2019info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:recercat.cat:10459.1/683042026-05-29T05:05:01Z
dc.title.none.fl_str_mv Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks
title Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks
spellingShingle Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks
Zapatka, Mariel
Smc5
Nse2
Mms21
SUMO
Mph1
DNA damage tolerance
Fork regression
DNA replication
Yeast
Chromosome
title_short Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks
title_full Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks
title_fullStr Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks
title_full_unstemmed Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks
title_sort Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks
dc.creator.none.fl_str_mv Zapatka, Mariel
Pociño Merino, Irene
Heluani-Gahete, Hayat
Bermúdez López, Marcelino
Tarrés Escalona, Marc
Ibars Estiarte, Eva Irene
Solé-Soler, Roger
Gutiérrez-Escribano, Pilar
Apostolova, Sonia
Casas Herranz, Celia
Aragon, Luis
Wellinger, Ralf Erik
Colomina i Gabarrella, Neus
Torres Rosell, Jordi
author Zapatka, Mariel
author_facet Zapatka, Mariel
Pociño Merino, Irene
Heluani-Gahete, Hayat
Bermúdez López, Marcelino
Tarrés Escalona, Marc
Ibars Estiarte, Eva Irene
Solé-Soler, Roger
Gutiérrez-Escribano, Pilar
Apostolova, Sonia
Casas Herranz, Celia
Aragon, Luis
Wellinger, Ralf Erik
Colomina i Gabarrella, Neus
Torres Rosell, Jordi
author_role author
author2 Pociño Merino, Irene
Heluani-Gahete, Hayat
Bermúdez López, Marcelino
Tarrés Escalona, Marc
Ibars Estiarte, Eva Irene
Solé-Soler, Roger
Gutiérrez-Escribano, Pilar
Apostolova, Sonia
Casas Herranz, Celia
Aragon, Luis
Wellinger, Ralf Erik
Colomina i Gabarrella, Neus
Torres Rosell, Jordi
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Smc5
Nse2
Mms21
SUMO
Mph1
DNA damage tolerance
Fork regression
DNA replication
Yeast
Chromosome
topic Smc5
Nse2
Mms21
SUMO
Mph1
DNA damage tolerance
Fork regression
DNA replication
Yeast
Chromosome
description Replication 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
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/10.1016/j.celrep.2019.10.123
http://hdl.handle.net/10459.1/68304
http://hdl.handle.net/10459.1/68304
url https://doi.org/10.1016/j.celrep.2019.10.123
http://hdl.handle.net/10459.1/68304
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//BFU2015-69183-P
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-097796-B-I00
Reproducció del document publicat a https://doi.org/10.1016/j.celrep.2019.10.123
Cell Reports, 2019, vol. 29, núm. 10, p. 3160-3172
dc.rights.none.fl_str_mv cc-by, (c) Zapatka et al., 2019
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv cc-by, (c) Zapatka et al., 2019
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,228081

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