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dc.contributor.authorAtashpaz, Sina
dc.contributor.authorSamadi Shams, Sara
dc.contributor.authorGonzalez, Javier Martin
dc.contributor.authorSebestyén, Endre
dc.contributor.authorArghavanifard, Negar
dc.contributor.authorGnocchi, Andrea
dc.contributor.authorAlbers, Eliene
dc.contributor.authorMinardi, Simone
dc.contributor.authorFaga, Giovanni
dc.contributor.authorSoffientini, Paolo
dc.contributor.authorAllievi, Elisa
dc.contributor.authorCancila, Valeria
dc.contributor.authorBachi, Angela
dc.contributor.authorTripodo, Claudio
dc.contributor.authorFerrari, Francesco
dc.contributor.authorLópez-Contreras, Andrés Joaquin
dc.contributor.authorCostanzo, Vincenzo
dc.contributor.authorFernandez-Capetillo, Oscar 
dc.date.accessioned2020-09-08T08:56:27Z
dc.date.available2020-09-08T08:56:27Z
dc.date.issued2020-03-12
dc.identifier.citationElife. 2020;9:e54756.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/10988
dc.descriptionFondazione Italiana per la Ricerca sul Cancro FIRC 18112 Sina Atashpaz.Fondazione Umberto Veronesi Sina Atashpaz Associazione Italiana per la Ricerca sul Cancro AIRC 5xmille METAMECH program Vincenzo Costanzo Giovanni Armenise-Harvard Foundation Vincenzo Costanzo European Research Council Consolidator grant 614541 Vincenzo Costanzo Associazione Italiana per la Ricerca sul Cancro Fellowship 23961 Negar ArghavanifarDanish Cancer Society KBVU-2014 Andres Joaquin Lopez-Contreras Danish Council for Independent Research Sapere Aude, DFF Starting Grant 2014 Andres Joaquin Lopez-Contreras European Research Council ERC-2015-STG-679068 Andres Joaquin Lopez-Contreras Danish National Research Foundation DNRF115 Andres Joaquin Lopez-Contreras The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.es_ES
dc.description.abstractUnrepaired DNA damage during embryonic development can be potentially inherited by a large population of cells. However, the quality control mechanisms that minimize the contribution of damaged cells to developing embryos remain poorly understood. Here, we uncovered an ATR- and CHK1-mediated transcriptional response to replication stress (RS) in mouse embryonic stem cells (ESCs) that induces genes expressed in totipotent two-cell (2C) stage embryos and 2C-like cells. This response is mediated by Dux, a multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals. In response to RS, DUX triggers the transcription of 2C-like markers such as murine endogenous retrovirus-like elements (MERVL) and Zscan4. This response can also be elicited by ETAA1-mediated ATR activation in the absence of RS. ATR-mediated activation of DUX requires GRSF1-dependent post-transcriptional regulation of Dux mRNA. Strikingly, activation of ATR expands ESCs fate potential by extending their contribution to both embryonic and extra-embryonic tissues. These findings define a novel ATR dependent pathway involved in maintaining genome stability in developing embryos by controlling ESCs fate in response to RS.es_ES
dc.language.isoenges_ES
dc.publishereLife Sciences Publications es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectDNA-DAMAGEes_ES
dc.subjectEPIGENETIC RESTRICTIONes_ES
dc.subjectTELOMERE ELONGATIONes_ES
dc.subjectGENOMIC STABILITYes_ES
dc.subjectGENE ATRes_ES
dc.titleATR expands embryonic stem cell fate potential in response to replication stress.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID32163370es_ES
dc.format.volume9es_ES
dc.identifier.doi10.7554/eLife.54756es_ES
dc.contributor.funderItalian Association for Cancer Research 
dc.contributor.funderGiovanni Armenise-Harvard Foundation 
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) 
dc.contributor.funderDanish Cancer Society 
dc.contributor.funderDet Frie Forskningsrad (DFF)
dc.contributor.funderDanish National Research Foundation 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2050-084Xes_ES
dc.relation.publisherversionhttps://doi.org/10.7554/eLife.54756.es_ES
dc.identifier.journaleLifees_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Inestabilidad Genómicaes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/EC/FP7/614541es_ES
dc.rights.accessRightsopen accesses_ES


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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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