Show simple item record

dc.contributor.authorMurga M, Matilde 
dc.contributor.authorLecona, Emilio
dc.contributor.authorKamileri, Irene
dc.contributor.authorDíaz, Marcos
dc.contributor.authorLugli, Natalia
dc.contributor.authorSotiriou, Sotirios K
dc.contributor.authorAnton, Marta E
dc.contributor.authorMendez, Juan 
dc.contributor.authorHalazonetis, Thanos D
dc.contributor.authorFernandez-Capetillo, Oscar 
dc.date.accessioned2019-10-23T09:52:04Z
dc.date.available2019-10-23T09:52:04Z
dc.date.issued2016-09-01
dc.identifier.citationMol Cell. 2016;63(5):877-83.es_ES
dc.identifier.issn10972765es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8527
dc.description.abstractThe Pold3 gene encodes a subunit of the Polδ DNA polymerase complex. Pold3 orthologs are not essential in Saccharomyces cerevisiae or chicken DT40 cells, but the Schizosaccharomyces pombe ortholog is essential. POLD3 also has a specialized role in the repair of broken replication forks, suggesting that POLD3 activity could be particularly relevant for cancer cells enduring high levels of DNA replication stress. We report here that POLD3 is essential for mouse development and is also required for viability in adult animals. Strikingly, even Pold3(+/-) mice were born at sub-Mendelian ratios, and, of those born, some presented hydrocephaly and had a reduced lifespan. In cells, POLD3 deficiency led to replication stress and cell death, which were aggravated by the expression of activated oncogenes. Finally, we show that Pold3 deletion destabilizes all members of the Polδ complex, explaining its major role in DNA replication and the severe impact of its deficiency.es_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) (SAF2014-59498-R; SAF2014-57791-REDC), 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 Fellowshp (IOF) from the FP7 Marie Curie Actions and a grant from MINECO (BFU2014-55168-JIN) that was co-funded by European Regional Development Funds (FEDER) to E.L.; by a grant from MINECO (BFU2013-49153) to J.M.; and by the European Commission (ERC grant ONIDDAC) to T.D.H.es_ES
dc.language.isoenges_ES
dc.publisherCell Presses_ES
dc.relation.isversionofPostprintes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshB-Lymphocytes es_ES
dc.subject.meshBrain es_ES
dc.subject.meshCell Death es_ES
dc.subject.meshCheckpoint Kinase 1 es_ES
dc.subject.meshDNA Damage es_ES
dc.subject.meshDNA Polymerase III es_ES
dc.subject.meshGene Expression Regulation, Developmental es_ES
dc.subject.meshHistones es_ES
dc.subject.meshHomozygote es_ES
dc.subject.meshHydrocephalus es_ES
dc.subject.meshLongevity es_ES
dc.subject.meshLung es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshPhosphorylation es_ES
dc.subject.meshSurvival Analysis es_ES
dc.subject.meshDNA Replication es_ES
dc.subject.meshHaploinsufficiency es_ES
dc.titlePOLD3 Is Haploinsufficient for DNA Replication in Micees_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID27524497es_ES
dc.format.volume63es_ES
dc.format.number5es_ES
dc.format.page877-83es_ES
dc.identifier.doi10.1016/j.molcel.2016.07.007es_ES
dc.contributor.funderFundacion Botínes_ES
dc.contributor.funderBanco Santanderes_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderFundacion La Mataroes_ES
dc.contributor.funderHoward Hughes Medical Institutees_ES
dc.contributor.funderEuropean Research Council (ERC)es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1097-4164es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.molcel.2016.07.007.es_ES
dc.identifier.journalMolecular celles_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Inestabilidad Genómicaes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2014-59498-Res_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2014-57791-REDCes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/BFU2014-55168-JINes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/BFU2013-49153es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


Files in this item

Acceso Abierto
Acceso Abierto
Thumbnail
Acceso Abierto
Thumbnail
Acceso Abierto

This item appears in the following Collection(s)

Show simple item record

Atribución-NoComercial-CompartirIgual 4.0 Internacional
This item is licensed under a: Atribución-NoComercial-CompartirIgual 4.0 Internacional