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dc.contributor.authorMitxelena, Jone
dc.contributor.authorApraiz, Aintzane
dc.contributor.authorVallejo-Rodríguez, Jon
dc.contributor.authorGarcía-Santisteban, Iraia
dc.contributor.authorFullaondo, Asier
dc.contributor.authorAlvarez Fernandez, Monica 
dc.contributor.authorMalumbres Martinez, Marcos 
dc.contributor.authorZubiaga, Ana M
dc.date.accessioned2018-10-29T12:53:48Z
dc.date.available2018-10-29T12:53:48Z
dc.date.issued2018-05-18
dc.identifier.citationNucleic Acids Res. 2018; 46 (9): 4546 - 4559.es_ES
dc.identifier.issn0305-1048es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6550
dc.description.abstractThe cellular response to DNA damage is essential for maintaining the integrity of the genome. Recent evidence has identified E2F7 as a key player in DNA damage-dependent transcriptional regulation of cell-cycle genes. However, the contribution of E2F7 to cellular responses upon genotoxic damage is still poorly defined. Here we show that E2F7 represses the expression of genes involved in the maintenance of genomic stability, both throughout the cell cycle and upon induction of DNA lesions that interfere with replication fork progression. Knockdown of E2F7 leads to a reduction in 53BP1 and FANCD2 foci and to fewer chromosomal aberrations following treatment with agents that cause interstrand crosslink (ICL) lesions but not upon ionizing radiation. Accordingly, E2F7-depleted cells exhibit enhanced cell-cycle re-entry and clonogenic survival after exposure to ICL-inducing agents. We further report that expression and functional activity of E2F7 are p53-independent in this context. Using a cell-based assay, we show that E2F7 restricts homologous recombination through the transcriptional repression of RAD51. Finally, we present evidence that downregulation of E2F7 confers an increased resistance to chemotherapy in recombination-deficient cells. Taken together, our results reveal an E2F7-dependent transcriptional program that contributes to the regulation of DNA repair and genomic integrity.es_ES
dc.description.sponsorshipWe thank members of the Zubiaga and Malumbres labo- ratory for helpful discussions, Naiara Zorrilla for technical support, Jose Antonio Rodrıguez for critical reading of the manuscript, D. Olmos and J. Surrall ́es for kindly providing cell lines and R. Medema for providing CRISPR /Cas9 plas- mids.es_ES
dc.language.isoenges_ES
dc.publisherOxford University Press es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCROSS-LINK REPAIRes_ES
dc.subjectNUCLEOTIDE EXCISION-REPAIRes_ES
dc.subjectFANCONI-ANEMIA PATHWAYes_ES
dc.subjectDOUBLE-STRAND BREAKSes_ES
dc.subjectCELL-CYCLE GENESes_ES
dc.subjectOMOLOGOUS RECOMBINATIONes_ES
dc.subjectMELPHALAN RESISTANCEes_ES
dc.subjectMAMMALIAN-CELLSes_ES
dc.subjectE2Fes_ES
dc.subjectSITESes_ES
dc.titleAn E2F7-dependent transcriptional program modulates DNA damage repair and genomic stabilityes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29590434es_ES
dc.format.volume46es_ES
dc.format.number9es_ES
dc.format.page4546-4559es_ES
dc.identifier.doi10.1093/nar/gky218es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.contributor.funderBasque Government (España) 
dc.contributor.funderUniversity of the Basque Country (España) 
dc.contributor.funderWorldwide Cancer Research 
dc.description.peerreviewed
dc.identifier.e-issn1362-4962es_ES
dc.relation.publisherversionhttps://doi.org/doi: 10.1093/nar/gky218es_ES
dc.identifier.journalNucleic acids researches_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigaciónes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de División Celular y Cánceres_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-67562-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-57791-REDCes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-69920-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-60442-JINes_ES
dc.rights.accessRightsopen accesses_ES


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