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http://hdl.handle.net/10261/221235
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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Álvarez-Quilón, Alejandro | es_ES |
dc.contributor.author | Terrón-Bautista, José | es_ES |
dc.contributor.author | Delgado, Irene | es_ES |
dc.contributor.author | Serrano-Benítez, Almudena | es_ES |
dc.contributor.author | Romero-Granados, Rocío | es_ES |
dc.contributor.author | Martínez-García, Pedro Manuel | es_ES |
dc.contributor.author | Jimeno-González, Silvia | es_ES |
dc.contributor.author | Bernal-Lozano, Cristina | es_ES |
dc.contributor.author | Quintero, Cristina | es_ES |
dc.contributor.author | García-Quintanilla, Lourdes | es_ES |
dc.contributor.author | Cortés-Ledesma, Felipe | es_ES |
dc.date.accessioned | 2020-10-15T09:56:00Z | - |
dc.date.available | 2020-10-15T09:56:00Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Nature Communications 11: 910 (2020) | es_ES |
dc.identifier.uri | http://hdl.handle.net/10261/221235 | - |
dc.description.abstract | The ATM kinase is a master regulator of the DNA damage response to double-strand breaks (DSBs) and a well-established tumour suppressor whose loss is the cause of the neurodegenerative and cancer-prone syndrome Ataxia-Telangiectasia (A-T). A-T patients and Atm−/− mouse models are particularly predisposed to develop lymphoid cancers derived from deficient repair of RAG-induced DSBs during V(D)J recombination. Here, we unexpectedly find that specifically disturbing the repair of DSBs produced by DNA topoisomerase II (TOP2) by genetically removing the highly specialised repair enzyme TDP2 increases the incidence of thymic tumours in Atm−/− mice. Furthermore, we find that TOP2 strongly colocalizes with RAG, both genome-wide and at V(D)J recombination sites, resulting in an increased endogenous chromosomal fragility of these regions. Thus, our findings demonstrate a strong causal relationship between endogenous TOP2-induced DSBs and cancer development, confirming these lesions as major drivers of ATM-deficient lymphoid malignancies, and potentially other conditions and cancer types. | es_ES |
dc.description.sponsorship | This work has been funded with grants from the Spanish and Andalusian Government (SAF2010-21017, SAF2013-47343-P, SAF2014-55532-R, SAF2017-89619-R, CVI-7948, European Regional Development Fund), and the European Research Council (ERC-CoG-2014-647359); and with individual fellowships for AAQ (Formación Personal Investigador, BES-2011-047351, Ministerio de Ciencia e Innovación), JTB (Formación Profesorado Universitario, FPU15/03656, Ministerio de Educación, Cultura y Deporte) and ASB (Beca Predoctoral AEFAT, Asociación Española Familia Ataxia Telangiectasia). CABIMER is supported by the Andalusian Government. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer Nature | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-47343-P | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-55532-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF2017-89619-R | es_ES |
dc.relation | SAF2017-89619-R/AEI/10.13039/501100011033 | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/647359 | es_ES |
dc.relation.isversionof | Publisher's version | es_ES |
dc.rights | openAccess | es_ES |
dc.title | Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency | es_ES |
dc.type | artículo | es_ES |
dc.identifier.doi | 10.1038/s41467-020-14638-w | - |
dc.description.peerreviewed | Peer reviewed | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/s41467-020-14638-w | es_ES |
dc.identifier.e-issn | 2041-1723 | - |
dc.rights.license | http://creativecommons.org/licenses/by/4.0/ | es_ES |
dc.contributor.funder | Junta de Andalucía | es_ES |
dc.contributor.funder | Agencia Estatal de Investigación (España) | es_ES |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | es_ES |
dc.contributor.funder | European Commission | es_ES |
dc.contributor.funder | European Research Council | es_ES |
dc.contributor.funder | Ministerio de Educación, Cultura y Deporte (España) | es_ES |
dc.contributor.funder | Asociación Española Familia Ataxia Telangiectasia | es_ES |
dc.relation.csic | Sí | es_ES |
oprm.item.hasRevision | no ko 0 false | * |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003176 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000781 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000780 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100011033 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100011011 | es_ES |
dc.identifier.pmid | 32060399 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | With Fulltext | - |
item.languageiso639-1 | en | - |
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