Publication:
USP7 is a SUMO deubiquitinase essential for DNA replication.

Simple item page
dc.contributor.authorLecona, Emilio
dc.contributor.authorRodriguez-Acebes, Sara
dc.contributor.authorSpecks, Julia
dc.contributor.authorLopez-Contreras, Andres J
dc.contributor.authorRuppen, Isabel
dc.contributor.authorMurga, Matilde
dc.contributor.authorMuñoz, Javier
dc.contributor.authorMendez, Juan
dc.contributor.authorFernandez-Capetillo, Oscar
dc.contributor.funderWorldwide Cancer Research
dc.contributor.funderFundación La Marató TV3
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC)
dc.contributor.funderDanish Council for Independent Research
dc.contributor.funderDanish National Research Foundation
dc.contributor.funderHoward Hughes Medical Institute
dc.contributor.funderBotín Foundation
dc.contributor.funderDanish Cancer Society
dc.date.accessioned2024-02-09T09:46:08Z
dc.date.available2024-02-09T09:46:08Z
dc.date.issued2016-04
dc.descriptionand SAF2014-57791-REDC)es_ES
dc.description.abstractPost-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment is maintained at sites of DNA replication in mammalian cells remains unexplored. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Inhibition or genetic deletion of USP7 leads to the accumulation of Ub on SUMOylated proteins, which are displaced away from replisomes. Our findings provide a model explaining the differential accumulation of SUMO and Ub at replication forks and identify an essential role of USP7 in DNA replication that should be considered in the development of USP7 inhibitors as anticancer agents.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipResearch was funded by Fundacion Botin, Banco Santander, through its Santander Universities Global Division, and by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2011-23753 and SAF2014-57791-REDC), Worldwide Cancer Research (12-0229), Fundacio La Marato de TV3, the Howard Hughes Medical Institute and the European Research Council (ERC-617840) to O.F.-C.; by a Marie-Curie International Outgoing Fellowship (project no. 235705) from the Seventh Framework Programme for Research and Technological Development, Marie Curie Actions, and a grant from MINECO (BFU2014-55168-JIN) that was cofunded by European Regional Development Funds (FEDER) to E.L.; by grants from the Danish Council for Independent Research and the Danish National Research Foundation to A.J.L.-C.; and by a PhD fellowship from MINECO (BES-2012-05 2030) to J.S. We would like to thank W. Gu (Columbia University) for providing Usp7lox/lox MEFs, J. Chen (MD Anderson Cancer Center) for providing Rad18-deficient HCT116 cells and J. Alegre-Cebollada (Spanish National Center for Cardiovascular Research) for help in the use of PyMOL software.es_ES
dc.format.number4es_ES
dc.format.page270es_ES
dc.format.volume23es_ES
dc.identifierhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869841/
dc.identifier
dc.identifier.citationNat Struct Mol Biol . 2016;23(4):270-7es_ES
dc.identifier.doi10.1038/nsmb.3185es_ES
dc.identifier.e-issn1545-9985es_ES
dc.identifier.journalNature structural & molecular biologyes_ES
dc.identifier.pubmedID26950370es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/17681
dc.language.isoenges_ES
dc.publisherNature Publishing Group
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/SAF2011-23753es_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/SAF2014-57791-REDCes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/617840/EUes_ES
dc.relation.publisherversionhttps://doi.org/10.1038/nsmb.3185es_ES
dc.repisalud.institucionCNIOes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshDNA Replicationes_ES
dc.subject.meshDNA Damagees_ES
dc.subject.meshDNA Repaires_ES
dc.subject.meshHCT116 Cellses_ES
dc.subject.meshHeLa Cellses_ES
dc.subject.meshHumanses_ES
dc.subject.meshModels, Moleculares_ES
dc.subject.meshSmall Ubiquitin-Related Modifier Proteinses_ES
dc.subject.meshSumoylationes_ES
dc.subject.meshUbiquitin Thiolesterasees_ES
dc.subject.meshUbiquitin-Specific Peptidase 7es_ES
dc.subject.meshUbiquitin-Specific Proteaseses_ES
dc.subject.meshUbiquitinationes_ES
dc.titleUSP7 is a SUMO deubiquitinase essential for DNA replication.es_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
relation.isAuthorOfPublicationafbc105a-c452-4690-9445-4f431b00f195
relation.isAuthorOfPublication109ab297-8df3-458e-9a03-0dd210ea8e09
relation.isAuthorOfPublication8aba2c75-fe8e-4a3a-be8b-baae02fb66d8
relation.isAuthorOfPublicationeb478d8c-dd11-4b47-8795-7ac57cb60b2d
relation.isAuthorOfPublication.latestForDiscoveryafbc105a-c452-4690-9445-4f431b00f195
relation.isFunderOfPublicationa24641d2-70e0-46bf-85bd-438762d90c59
relation.isFunderOfPublicationff637ff5-6bbe-4cb4-917f-84200711c119
relation.isFunderOfPublicationcb2ee04a-8d42-4a64-b3f6-3c156f222b35
relation.isFunderOfPublication85877f50-f113-467c-8ae9-fe28bf4af2dc
relation.isFunderOfPublicationa91e182c-634f-4e3a-9868-33f0e2cf1d31
relation.isFunderOfPublication7415ef7c-a300-4053-869f-70eea45dcde7
relation.isFunderOfPublication16a4a4c1-5edb-4ef6-b9e5-e3861bf4fc84
relation.isFunderOfPublication96cb099b-504f-4011-8a51-a38f8c21e660
relation.isFunderOfPublication.latestForDiscoverya24641d2-70e0-46bf-85bd-438762d90c59
relation.isPublisherOfPublication301fb00e-338e-4f8c-beaa-f9d8f4fefcc0
relation.isPublisherOfPublication.latestForDiscovery301fb00e-338e-4f8c-beaa-f9d8f4fefcc0

Files

Collections

Grupos de investigación