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dc.contributor.author | Jacome, Ariana | |
dc.contributor.author | Gutierrez-Martinez, Paula | |
dc.contributor.author | Schiavoni, Federica | |
dc.contributor.author | Tenaglia, Enrico | |
dc.contributor.author | Martinez, Paula | |
dc.contributor.author | Rodríguez-Acebes, Sara | |
dc.contributor.author | Lecona, Emilio | |
dc.contributor.author | Murga, Matilde | |
dc.contributor.author | Mendez, Juan | |
dc.contributor.author | Blasco, MA | |
dc.contributor.author | Fernandez-Capetillo, Oscar | |
dc.date.accessioned | 2024-04-24T05:49:23Z | |
dc.date.available | 2024-04-24T05:49:23Z | |
dc.date.issued | 2015-11-03 | |
dc.identifier.citation | EMBO J . 2015 3;34(21):2604-19 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/19190 | |
dc.description.abstract | The SMC5/6 complex is the least understood of SMC complexes. In yeast, smc5/6 mutants phenocopy mutations in sgs1, the BLM ortholog that is deficient in Bloom's syndrome (BS). We here show that NSMCE2 (Mms21, in Saccharomyces cerevisiae), an essential SUMO ligase of the SMC5/6 complex, suppresses cancer and aging in mice. Surprisingly, a mutation that compromises NSMCE2-dependent SUMOylation does not have a detectable impact on murine lifespan. In contrast, NSMCE2 deletion in adult mice leads to pathologies resembling those found in patients of BS. Moreover, and whereas NSMCE2 deletion does not have a detectable impact on DNA replication, NSMCE2-deficient cells also present the cellular hallmarks of BS such as increased recombination rates and an accumulation of micronuclei. Despite the similarities, NSMCE2 and BLM foci do not colocalize and concomitant deletion of Blm and Nsmce2 in B lymphocytes further increases recombination rates and is synthetic lethal due to severe chromosome mis-segregation. Our work reveals that SUMO- and BLM-independent activities of NSMCE2 limit recombination and facilitate segregation; functions of the SMC5/6 complex that are necessary to prevent cancer and aging in mice. | es_ES |
dc.description.sponsorship | The authors want to thank Jordi Torres and Mark O'Driscoll for comments on the manuscript. Work in OF laboratory related to this project was supported by Fundacion Botin, by Banco Santander through its Santander Universities Global Division and by grants from MINECO (SAF2011-23753 and SAF2014-57791-REDC), Howard Hughes Medical Institute, and the European Research Council (ERC-617840). Work in JM laboratory was funded by a grant from MINECO (BFU2013-49153P). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | EMBO Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Aging | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | B-Lymphocytes | es_ES |
dc.subject.mesh | Base Sequence | es_ES |
dc.subject.mesh | Cells, Cultured | es_ES |
dc.subject.mesh | Chromosome Segregation | es_ES |
dc.subject.mesh | DNA Breaks, Double-Stranded | es_ES |
dc.subject.mesh | DNA Mutational Analysis | es_ES |
dc.subject.mesh | DNA Replication | es_ES |
dc.subject.mesh | Female | es_ES |
dc.subject.mesh | Haploinsufficiency | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Ligases | es_ES |
dc.subject.mesh | Mice, 129 Strain | es_ES |
dc.subject.mesh | Mice, Inbred C57BL | es_ES |
dc.subject.mesh | Mice, Knockout | es_ES |
dc.subject.mesh | Neoplasms | es_ES |
dc.subject.mesh | Protein Transport | es_ES |
dc.subject.mesh | RecQ Helicases | es_ES |
dc.subject.mesh | Sumoylation | es_ES |
dc.subject.mesh | Tumor Suppressor Proteins | es_ES |
dc.subject.mesh | Ubiquitin-Protein Ligases | es_ES |
dc.title | NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 26443207 | es_ES |
dc.format.volume | 34 | es_ES |
dc.format.number | 21 | es_ES |
dc.format.page | 2604 | es_ES |
dc.identifier.doi | 10.15252/embj.201591829 | es_ES |
dc.contributor.funder | Fundacion Botin | es_ES |
dc.contributor.funder | Banco Santander | es_ES |
dc.contributor.funder | Howard Hughes Medical Institute | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | es_ES |
dc.contributor.funder | Worldwide Cancer Research | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1460-2075 | es_ES |
dc.relation.publisherversion | https://doi.org/10.15252/embj.201591829 | es_ES |
dc.identifier.journal | The EMBO journal | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Inestabilidad Genómica | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/617840/EU | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/SAF2014-57791-REDC | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/SAF2011-23753 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/BFU2013-49153P | es_ES |