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Major roles for pyrimidine dimers, nucleotide excision repair, and ATR in the alternative splicing response to UV irradiation

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dc.contributor.author Muñoz, Manuel Javier
dc.contributor.author Nieto Moreno, Nicolás
dc.contributor.author Giono, Luciana E.
dc.contributor.author Cambindo Botto, Adrián E.
dc.contributor.author Dujardin, Gwendal
dc.contributor.author Bastianello, Giulia
dc.contributor.author Lavore, Stefania
dc.contributor.author Torres Méndez, Antonio
dc.contributor.author Menck, Carlos Frederico Martins
dc.contributor.author Blencowe, Benjamin J.
dc.contributor.author Irimia Martínez, Manuel
dc.contributor.author Foiani, Marco
dc.contributor.author Kornblihtt, Alberto R.
dc.date.accessioned 2018-05-23T13:46:20Z
dc.date.available 2018-05-23T13:46:20Z
dc.date.issued 2017
dc.identifier.citation Muñoz MJ, Nieto Moreno N, Giono LE, Cambindo Botto AE, Dujardin G, Bastianello G et al. Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation. Cell Rep. 2017 Mar;18(12):2868-79. DOI: 10.1016/j.celrep.2017.02.066
dc.identifier.issn 2211-1247
dc.identifier.uri http://hdl.handle.net/10230/34709
dc.description.abstract We have previously found that UV irradiation promotes RNA polymerase II (RNAPII) hyperphosphorylation and subsequent changes in alternative splicing (AS). We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of the most abundant class of pyrimidine dimers (PDs) abrogates the global response to UV. We demonstrate that, in keratinocytes, RNAPII is the target, but not a sensor, of the signaling cascade initiated by PDs. The UV effect is enhanced by inhibition of gap-filling DNA synthesis, the last step in the nucleotide excision repair pathway (NER), and reduced by the absence of XPE, the main NER sensor of PDs. The mechanism involves activation of the protein kinase ATR that mediates the UV-induced RNAPII hyperphosphorylation. Our results define the sequence UV-PDs-NER-ATR-RNAPII-AS as a pathway linking DNA damage repair to the control of both RNAPII phosphorylation and AS regulation.
dc.description.sponsorship A.R.K. and M.J.M. received support from the Agencia Nacional de Promoción Científica y Tecnológica of Argentina (PICT-2011 1617, PICT-2014 2582), the Universidad de Buenos Aires (UBACYT 20020130100152BA), and the Alberto J. Roemmers Foundation. G.D. was supported by Marie Curie International Outgoing Fellowship within the EU Seventh Framework Programme for Research and Technological Development (FP7/2007-2013) under grant agreement 275632. B.J.B. is supported by grants from the Canadian Institutes of Health Research (FDN 148434). M.I. is supported by grants from the European Research Council (ERC-StG-LS2- 637591) and from Ministerio de Economía y Competitividad (BFU2014-55076-P; MINECO). A.T.-M. is supported by an FPI-SO fellowship from the Spanish Ministry of Economy and Competitiveness. M.F. is supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) and Telethon-Italy. G.B. is recipient of a fellowship from the University of Milan. S.L. is an employee of IFOM Cell Biology Unit. M.J.M., L.E.G., and A.R.K. are career investigators and N.N.M. and A.E.C.B. are recipients of a graduate student fellowship from the Consejo Nacional de Investigaciones Científicas y Técnicas of Argentina (CONICET). A.R.K. is a Senior International Research Scholar of the Howard Hughes Medical Institute.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Cell Reports. 2017 Mar;18(12):2868-79
dc.rights © 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title Major roles for pyrimidine dimers, nucleotide excision repair, and ATR in the alternative splicing response to UV irradiation
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2017.02.066
dc.subject.keyword ATR
dc.subject.keyword DNA damage
dc.subject.keyword Potorous photolyase
dc.subject.keyword UV irradiation
dc.subject.keyword Alternative splicing
dc.subject.keyword Cyclobutane pyrimidine dimers
dc.subject.keyword Global genome repair
dc.subject.keyword Nucleotide excision repair
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/275632
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/637591
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55076-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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