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dc.contributor.authorGavish-Izakson, Michales_ES
dc.contributor.authorVelpula, Bhagya Bhavanaes_ES
dc.contributor.authorElkon, Ranes_ES
dc.contributor.authorPrados-Carvajal, Rosarioes_ES
dc.contributor.authorBarnabas, Georgina D.es_ES
dc.contributor.authorPineiro Ugalde, Alejandroes_ES
dc.contributor.authorAgami, Reuvenes_ES
dc.contributor.authorGeiger, Tamares_ES
dc.contributor.authorHuertas Sánchez, Pabloes_ES
dc.contributor.authorZiv, Yaeles_ES
dc.contributor.authorShiloh, Yosefes_ES
dc.date.accessioned2019-04-25T08:55:06Z-
dc.date.available2019-04-25T08:55:06Z-
dc.date.issued2018-01-25-
dc.identifier.citationNucleic Acids Research 46(2): 3351–3365 (2018)es_ES
dc.identifier.issn0305-1048-
dc.identifier.urihttp://hdl.handle.net/10261/180525-
dc.description.abstractThe DNA damage response (DDR) is an extensive signaling network that is robustly mobilized by DNA double-strand breaks (DSBs). The primary transducer of the DSB response is the protein kinase, ataxia-telangiectasia, mutated (ATM). Here, we establish nuclear poly(A)-binding protein 1 (PABPN1) as a novel target of ATM and a crucial player in the DSB response. PABPN1 usually functions in regulation of RNA processing and stability. We establish that PABPN1 is recruited to the DDR as a critical regulator of DSB repair. A portion of PABPN1 relocalizes to DSB sites and is phosphorylated on Ser95 in an ATM-dependent manner. PABPN1 depletion sensitizes cells to DSB-inducing agents and prolongs the DSB-induced G2/M cell-cycle arrest, and DSB repair is hampered by PABPN1 depletion or elimination of its phosphorylation site. PABPN1 is required for optimal DSB repair via both nonhomologous end-joining (NHEJ) and homologous recombination repair (HRR), and specifically is essential for efficient DNA-end resection, an initial, key step in HRR. Using mass spectrometry analysis, we capture DNA damage-induced interactions of phospho-PABPN1, including well-established DDR players as well as other RNA metabolizing proteins. Our results uncover a novel ATM-dependent axis in the rapidly growing interface between RNA metabolism and the DDRes_ES
dc.description.sponsorshipWork in Y.S. laboratory is funded by research grants from the Dr Miriam and Sheldon G. Adelson Medical Research Foundation; The A-T Children's Project; The Israel Science Foundation (Joint ISF-NSFC Program with the National Natural Science Foundation of China); The Israel Cancer Research Fund; Work in P.H. lab was supported by R+D+I grant from the Spanish Ministry of Economy and Competitivity [SAF2013-43255-P]; ERC Starting Grant [DSBRECA]; PhD fellowship from the Spanish Ministry of Education (FPU to R.P.-C.); The R.A. lab is supported by NWO grant [NGI 93512001 to R.A.]; The Human Frontier Science Program [LT000640/2013 to A.P.U.]; The work in T.G. lab was supported by The I-CORE Program of the Planning and Budgeting Committee of the Israel Ministry of Education; Y.S. is a Research Professor of the Israel Cancer Research Fund. Funding for open access charge: research grant money.es_ES
dc.language.isoenges_ES
dc.publisherOxford University Presses_ES
dc.relationMINECO/ICTI2013-2016/SAF2013-43255-Pes_ES
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/278867es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rightsopenAccesses_ES
dc.titleNuclear poly(A)-binding protein 1 is an ATM target and essential for DNA double-strand break repaires_ES
dc.typeartículoes_ES
dc.identifier.doi10.1093/nar/gkx1240-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.1093/nar/gkx1240es_ES
dc.identifier.e-issn1362-4962-
dc.rights.licensehttp://creativecommons.org/licenses/by/4.0/es_ES
dc.contributor.funderAdelson Medical Research Foundationes_ES
dc.contributor.funderA-T Children's Projectes_ES
dc.contributor.funderIsrael Science Foundationes_ES
dc.contributor.funderNational Natural Science Foundation of Chinaes_ES
dc.contributor.funderIsrael Cancer Research Fundes_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderEuropean Research Counciles_ES
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España)es_ES
dc.contributor.funderNetherlands Organization for Scientific Researches_ES
dc.contributor.funderHuman Frontier Science Programes_ES
dc.contributor.funderMinistry of Education (Israel)es_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/100001962es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100004412es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003176es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100005984es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000781es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100001809es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100001698es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003977es_ES
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