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dc.contributor.authorPacheco, Sarai
dc.contributor.authorMaldonado-Linares, Andros
dc.contributor.authorMarcet-Ortega, Marina
dc.contributor.authorRojas, Cristina
dc.contributor.authorMartínez-Marchal, Ana
dc.contributor.authorFuentes-Lazaro, Judit
dc.contributor.authorLange, Julian
dc.contributor.authorJasin, Maria
dc.contributor.authorKeeney, Scott
dc.contributor.authorFernandez-Capetillo, Oscar 
dc.contributor.authorGarcia-Caldés, Montserrat
dc.contributor.authorRoig, Ignasi
dc.date.accessioned2019-09-16T10:27:58Z
dc.date.available2019-09-16T10:27:58Z
dc.date.issued2018-07-05
dc.identifier.citationNat Commun. 2018;9(1):2622.es_ES
dc.identifier.issn2041-1723es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8349
dc.description.abstractPrecise execution of recombination during meiosis is essential for forming chromosomally-balanced gametes. Meiotic recombination initiates with the formation and resection of DNA double-strand breaks (DSBs). Cellular responses to meiotic DSBs are critical for efficient repair and quality control, but molecular features of these remain poorly understood, particularly in mammals. Here we report that the DNA damage response protein kinase ATR is crucial for meiotic recombination and completion of meiotic prophase in mice. Using a hypomorphic Atr mutation and pharmacological inhibition of ATR in vivo and in cultured spermatocytes, we show that ATR, through its effector kinase CHK1, promotes efficient RAD51 and DMC1 assembly at RPA-coated resected DSB sites and establishment of interhomolog connections during meiosis. Furthermore, our findings suggest that ATR promotes local accumulation of recombination markers on unsynapsed axes during meiotic prophase to favor homologous chromosome synapsis. These data reveal that ATR plays multiple roles in mammalian meiotic recombination.es_ES
dc.description.sponsorshipWe thank M. A. Handel (The Jackson Laboratory, Bar Harbor, USA) for the anti-H1T antibody; E. Marcon for the anti-RPA antibody (University of Toronto, Canada); A. Toth for the anti-pHORMAD2 antibody (U. Dresden, Germany) and N. Hunter for the anti- RNF212 antibody (UC Davis, USA); J. Turner (National Institute for Medical Research,London, UK) for assistance in the RNA-FISH experiments, for the X chromosome probe,for providing AtrFL/−testis samples and for sharing unpublished data; L. Kauppi(University of Helsinki, Finland) for providing us with protocols for the testis cultures;and members of the Roig lab and the Spanish Ministerio de Ciencia e Innovación-funded Network of Spanish groups working on Meiosis (MeioNet, BFU201‐71786‐REDT) and Enrique Martínez Pérez (Imperial College, London, UK) for helpful discussions. M.M.O. was supported by a FPI fellowship from the Ministerio de Ciencia e Innovación (BES-2011-045381). J.L. was supported in part by American Cancer Society post-doctoral fellowship (PF-12-157-01-DMC). S.K. is an Investigator of the Howard Hughes Medical Institute. This work was supported by the Ministerio de Ciencia e Innovación (BFU2010-18965, BFU2013-43965-P and BFU2016-80370-P, I.R.), by the UAB-Aposta award to young investigators (APOSTA2011-03, I.R.) and by the NIH (R35 GM118175, to M.J.and R35 GM118092 to S.K.).es_ES
dc.language.isoenges_ES
dc.publisherNATURE PUBLISHING GROUPes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshAtaxia Telangiectasia Mutated Proteins es_ES
dc.subject.meshCell Cycle Proteins es_ES
dc.subject.meshCheckpoint Kinase 1 es_ES
dc.subject.meshChromosome Pairing es_ES
dc.subject.meshIn Situ Hybridization, Fluorescence es_ES
dc.subject.meshMale es_ES
dc.subject.meshMeiosis es_ES
dc.subject.meshMice, 129 Strain es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshNuclear Proteins es_ES
dc.subject.meshRad51 Recombinase es_ES
dc.subject.meshSpermatocytes es_ES
dc.subject.meshTestis es_ES
dc.subject.meshDNA Breaks, Double-Stranded es_ES
dc.subject.meshHomologous Recombination es_ES
dc.titleATR is required to complete meiotic recombination in micees_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID29977027es_ES
dc.format.volume9es_ES
dc.format.number1es_ES
dc.format.page2622es_ES
dc.identifier.doi10.1038/s41467-018-04851-zes_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderAmerican Cancer Societyes_ES
dc.contributor.funderHoward Hughes Medical Institutees_ES
dc.contributor.funderNIHes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-018-04851-z.es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Inestabilidad Genómicaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2015-71786-REDTes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BES-2011-045381es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2010-18965es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2013-43965-Pes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2016-80370-Pes_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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