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Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice.

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dc.contributor.authorLopez-Contreras, Andres J
dc.contributor.authorSpecks, Julia
dc.contributor.authorBarlow, Jacqueline H
dc.contributor.authorAmbrogio, Chiara
dc.contributor.authorDesler, Claus
dc.contributor.authorVikingsson, Svante
dc.contributor.authorRodrigo-Perez, Sara
dc.contributor.authorGreen, Henrik
dc.contributor.authorRasmussen, Lene Juel
dc.contributor.authorNussenzweig, André
dc.contributor.authorFernandez-Capetillo, Oscar
dc.contributor.funderAsociación Española Contra el Cáncer
dc.contributor.funderSwedish Research Council
dc.contributor.funderBotín Foundation
dc.contributor.funderBanco Santander
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderWorldwide Cancer Research
dc.contributor.funderFundación La Marató TV3
dc.contributor.funderHoward Hughes Medical Institute
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC)
dc.contributor.funderDet Frie Forskningsrad (DFF)
dc.contributor.funderDanmarks Grundforskningsfond
dc.date.accessioned2020-06-03T15:26:31Z
dc.date.available2020-06-03T15:26:31Z
dc.date.issued2015-04-01
dc.description.abstractIn Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the RNR regulatory subunit RRM2 (Rrm2(TG)) present supraphysiological RNR activity and reduced chromosomal breakage at fragile sites. Moreover, increased Rrm2 gene dosage significantly extends the life span of ATR mutant mice. Our study reveals the first genetic condition in mammals that reduces fragile site expression and alleviates the severity of a progeroid disease by increasing RNR activity.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipA.J.L.-C. and C.A. were funded a post-doctoral fellowship from the Spanish Association for Cancer Research (AECC). J.S. is a recipient of a predoctoral fellowship from the Spanish government (BES-2012-05 2030). S.V. and H.G. are funded by the Swedish Research Council and the Swedish Cancer Society. Work in O.F.-C.'s laboratory was supported by Fundacion Botin, Banco Santander through its Santander Universities Global Division, and grants from Ministerio de Economia y Competitividad (MINECO; SAF2011-23753), Worldwide Cancer Research (12-0229), Fundacio La Marato de TV3, Howard Hughes Medical Institute, and the European Research Council (ERC-617840). Work in A.J.L.-C.'s laboratory is funded by the Danish Council for Independent Research (DFF) and the Danish National Research Foundatioes_ES
dc.format.number7es_ES
dc.format.page690-5es_ES
dc.format.volume29es_ES
dc.identifier.citationGenes Dev .2015 ;29(7):690-5.es_ES
dc.identifier.doi10.1101/gad.256958.114es_ES
dc.identifier.e-issn1549-5477es_ES
dc.identifier.journalGenes & developmentes_ES
dc.identifier.pubmedID25838540es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/10264
dc.language.isoenges_ES
dc.publisherCold Spring Harbor Laboratory Press
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2011-23753es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/EC/FP7/617840es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/BES-2012-05 2030es_ES
dc.relation.publisherversionhttps://doi.org/10.1101/gad.256958.114es_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Inestabilidad Genómicaes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshChromosome Breakagees_ES
dc.subject.meshAnimalses_ES
dc.subject.meshCell Linees_ES
dc.subject.meshCell Survivales_ES
dc.subject.meshCells, Culturedes_ES
dc.subject.meshChromosome Fragile Siteses_ES
dc.subject.meshEnzyme Activationes_ES
dc.subject.meshFibroblastses_ES
dc.subject.meshGene Dosagees_ES
dc.subject.meshHumanses_ES
dc.subject.meshLongevityes_ES
dc.subject.meshMicees_ES
dc.subject.meshNucleosideses_ES
dc.subject.meshProtein-Serine-Threonine Kinaseses_ES
dc.subject.meshRibonucleoside Diphosphate Reductasees_ES
dc.subject.meshSurvival Analysises_ES
dc.titleIncreased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice.es_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
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