Publication:
POLD3 Is Haploinsufficient for DNA Replication in Mice

Simple item page
dc.contributor.authorMurga, 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.contributor.funderBotín Foundation
dc.contributor.funderBanco Santander
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderFundación La Marató TV3
dc.contributor.funderHoward Hughes Medical Institute
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC)
dc.date.accessioned2019-10-23T09:52:04Z
dc.date.available2019-10-23T09:52:04Z
dc.date.issued2016-09-01
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.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) (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.format.number5es_ES
dc.format.page877-83es_ES
dc.format.volume63es_ES
dc.identifier.citationMol Cell. 2016;63(5):877-83.es_ES
dc.identifier.doi10.1016/j.molcel.2016.07.007es_ES
dc.identifier.e-issn1097-4164es_ES
dc.identifier.issn10972765es_ES
dc.identifier.journalMolecular celles_ES
dc.identifier.pubmedID27524497es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8527
dc.language.isoenges_ES
dc.publisherCell Press
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.relation.publisherversionhttps://doi.org/10.1016/j.molcel.2016.07.007.es_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.meshAnimalses_ES
dc.subject.meshB-Lymphocyteses_ES
dc.subject.meshBraines_ES
dc.subject.meshCell Deathes_ES
dc.subject.meshCheckpoint Kinase 1es_ES
dc.subject.meshDNA Damagees_ES
dc.subject.meshDNA Polymerase IIIes_ES
dc.subject.meshGene Expression Regulation, Developmentales_ES
dc.subject.meshHistoneses_ES
dc.subject.meshHomozygotees_ES
dc.subject.meshHydrocephaluses_ES
dc.subject.meshLongevityes_ES
dc.subject.meshLunges_ES
dc.subject.meshMicees_ES
dc.subject.meshMice, Knockoutes_ES
dc.subject.meshPhosphorylationes_ES
dc.subject.meshSurvival Analysises_ES
dc.subject.meshDNA Replicationes_ES
dc.subject.meshHaploinsufficiencyes_ES
dc.titlePOLD3 Is Haploinsufficient for DNA Replication in Micees_ES
dc.typejournal articlees_ES
dc.type.hasVersionAMes_ES
dspace.entity.typePublication
relation.isAuthorOfPublication109ab297-8df3-458e-9a03-0dd210ea8e09
relation.isAuthorOfPublication8aba2c75-fe8e-4a3a-be8b-baae02fb66d8
relation.isAuthorOfPublicationeb478d8c-dd11-4b47-8795-7ac57cb60b2d
relation.isAuthorOfPublication.latestForDiscovery109ab297-8df3-458e-9a03-0dd210ea8e09
relation.isFunderOfPublication16a4a4c1-5edb-4ef6-b9e5-e3861bf4fc84
relation.isFunderOfPublication2302598f-47dd-49b5-a26e-ae31bf61786e
relation.isFunderOfPublication77b2fc20-6311-4e46-98a7-83e46257b93b
relation.isFunderOfPublicationff637ff5-6bbe-4cb4-917f-84200711c119
relation.isFunderOfPublication7415ef7c-a300-4053-869f-70eea45dcde7
relation.isFunderOfPublicationcb2ee04a-8d42-4a64-b3f6-3c156f222b35
relation.isFunderOfPublication.latestForDiscovery16a4a4c1-5edb-4ef6-b9e5-e3861bf4fc84
relation.isPublisherOfPublicationaea619d1-42a6-47f8-84e2-6bc27d6f8300
relation.isPublisherOfPublication.latestForDiscoveryaea619d1-42a6-47f8-84e2-6bc27d6f8300

Files

Original bundle

Now showing 1 - 4 of 4
Thumbnail Image
Name:
PLANTILLA PREPINT REPOSITORIOS.pdf
Size:
30.41 KB
Format:
Adobe Portable Document Format
Download
Thumbnail Image
Name:
Pold3IsHaploinsufficientforDNA_2016.pdf
Size:
7.45 MB
Format:
Adobe Portable Document Format
Description:
Download
Thumbnail Image
Name:
Pold3IsHaploinsufficientforDNA_2016_supl.pdf
Size:
6.04 MB
Format:
Adobe Portable Document Format
Description:
Download
Thumbnail Image
Name:
Pold3IsHaploinsufficientforDNA_2016_table.pdf.xlsx
Size:
202.3 KB
Format:
Microsoft Excel XML
Description:
Download

Collections

Grupos de investigación