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dc.contributor.author | Alvarez-Prado, Angel Francisco | |
dc.contributor.author | Perez-Duran, Pablo | |
dc.contributor.author | Perez-Garcia, Arantxa | |
dc.contributor.author | Benguria, Alberto | |
dc.contributor.author | Torroja, Carlos | |
dc.contributor.author | de Yebenes, Virginia G | |
dc.contributor.author | Ramiro, Almudena R | |
dc.date.accessioned | 2018-10-26T07:59:28Z | |
dc.date.available | 2018-10-26T07:59:28Z | |
dc.date.issued | 2018 | |
dc.identifier | ISI:000440812100006 | |
dc.identifier.citation | J Exp Med. 2018; 215(3):761-771 | |
dc.identifier.issn | 0022-1007 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6545 | |
dc.description.abstract | Activation-induced deaminase (AID) initiates antibody diversification in germinal center (GC) B cells through the deamination of cytosines on immunoglobulin genes. AID can also target other regions in the genome, triggering mutations or chromosome translocations, with major implications for oncogenic transformation. However, understanding the specificity of AID has proved extremely challenging. We have sequenced at very high depth > 1,500 genomic regions from GC B cells and identified 275 genes targeted by AID, including 30 of the previously known 35 AID targets. We have also identified the most highly mutated hotspot for AID activity described to date. Furthermore, integrative analysis of the molecular features of mutated genes coupled to machine learning has produced a powerful predictive tool for AID targets. We also have found that base excision repair and mismatch repair back up each other to faithfully repair AID-induced lesions. Finally, our data establish a novel link between AID mutagenic activity and lymphomagenesis. | |
dc.description.sponsorship | A. Perez-Garcia was a fellow of the research training program funded by the Ministerio de Educacion, Cultura y Deporte (grant FPU-AP2009-1732); A.F. Alvarez-Prado and A.R. Ramiro are supported by Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC). This work was funded with the following grants to A.R. Ramiro from Plan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2013-2016, Programa Estatal de I+D+i Orientada a los Retos de la Sociedad Retos Investigacion: Proyectos I+D+i 2016, Ministerio de Economia, Industria y Competitividad (MEIC; grants SAF2013-42767-R and SAF2016-75511-R). This work is cofunded by Fondo Europeo de Desarrollo Regional and the European Research Council Starting Grant program (grant BCL YM-207844). The CNIC is supported by the MEIC and the Pro CNIC Foundation and is a Severo Ochoa Centre of Excellence (MEIC award SEV-2015-0505). | |
dc.language.iso | eng | |
dc.publisher | Rockefeller University Press | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | INDUCED CYTIDINE DEAMINASE | |
dc.subject | B-CELL LYMPHOMAS | |
dc.subject | CLASS SWITCH RECOMBINATION | |
dc.subject | SEQUENCING REVEALS | |
dc.subject | GENOMIC INSTABILITY | |
dc.subject | SUPER-ENHANCERS | |
dc.subject | DEFICIENT MICE | |
dc.subject | DNA BREAKS | |
dc.subject | IG GENES | |
dc.subject | C-MYC | |
dc.title | A broad atlas of somatic hypermutation allows prediction of activation-induced deaminase targets | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 29374026 | |
dc.format.volume | 215 | |
dc.format.page | 761-771 | |
dc.identifier.doi | 10.1084/jem.20171738 | |
dc.contributor.funder | Ministerio de Educación, Cultura y Deporte (España) | |
dc.contributor.funder | Ministerio de Economía, Industria y Competitividad (España) | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | |
dc.identifier.e-issn | 1540-9538 | |
dc.relation.publisherversion | https://doi.org/10.1084/jem.20171738 | |
dc.identifier.journal | Journal of Experimental Medicine | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Biología de linfocitos B | |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Bioinformática | |
dc.repisalud.institucion | CNIC | |
dc.rights.accessRights | open access | es_ES |