dc.contributor.author |
Hernández Viedma, Gonzalo |
dc.contributor.author |
Ramírez de Haro, Ma. José |
dc.contributor.author |
Minguillón Pedreño, Jordi |
dc.contributor.author |
Quiles, Paco |
dc.contributor.author |
Ruiz de Garibay, G. |
dc.contributor.author |
Aza-Carmona, Miriam |
dc.contributor.author |
Bogliolo, Massimo |
dc.contributor.author |
Pujol i Calvet, M. Roser |
dc.contributor.author |
Prados-Carvajal, Rosario |
dc.contributor.author |
Fernández-Rodríguez, Juana |
dc.contributor.author |
García, Nadia |
dc.contributor.author |
López, Adrià |
dc.contributor.author |
Gutiérrez-Enríquez, Sara |
dc.contributor.author |
Diez, Orland |
dc.contributor.author |
Benitez, Javier |
dc.contributor.author |
Salinas, Mónica |
dc.contributor.author |
Teulé, Àlex |
dc.contributor.author |
Brunet, Joan |
dc.contributor.author |
Radice, Paolo |
dc.contributor.author |
Peterlongo, Paolo |
dc.contributor.author |
Schindler, Detlev |
dc.contributor.author |
Huertas, Pablo |
dc.contributor.author |
Puente, Xose P. |
dc.contributor.author |
Lázaro, Coxi |
dc.contributor.author |
Pujana, Miguel Ángel |
dc.contributor.author |
Surrallés i Calonge, Jordi |
dc.date |
2018 |
dc.identifier |
https://ddd.uab.cat/record/188030 |
dc.identifier |
urn:10.1038/s41467-018-03433-3 |
dc.identifier |
urn:oai:ddd.uab.cat:188030 |
dc.identifier |
urn:pmid:29511213 |
dc.identifier |
urn:recercauab:ARE-87779 |
dc.identifier |
urn:scopus_id:85043264173 |
dc.identifier |
urn:wos_id:000426659600002 |
dc.identifier |
urn:altmetric_id:34018125 |
dc.identifier |
urn:oai:egreta.uab.cat:publications/7d27a086-f489-4dc3-aecb-412bd07671c5 |
dc.identifier |
urn:pmc-uid:5840268 |
dc.identifier |
urn:pmcid:PMC5840268 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:5840268 |
dc.description.abstract |
Altres ajuts: Surrallés laboratory is supported by the ICREA-Academia program and the Marató de TV3 (project 464/C/2012) |
dc.description.abstract |
BRCA1 is a tumor suppressor that regulates DNA repair by homologous recombination. Germline mutations in BRCA1 are associated with increased risk of breast and ovarian cancer and BRCA1 deficient tumors are exquisitely sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. Therefore, uncovering additional components of this DNA repair pathway is of extreme importance for further understanding cancer development and therapeutic vulnerabilities. Here, we identify EDC4, a known component of processing-bodies and regulator of mRNA decapping, as a member of the BRCA1-BRIP1-TOPBP1 complex. EDC4 plays a key role in homologous recombination by stimulating end resection at double-strand breaks. EDC4 deficiency leads to genome instability and hypersensitivity to DNA interstrand cross-linking drugs and PARP inhibitors. Lack-of-function mutations in EDC4 were detected in BRCA1/2-mutation-negative breast cancer cases, suggesting a role in breast cancer susceptibility. Collectively, this study recognizes EDC4 with a dual role in decapping and DNA repair whose inactivation phenocopies BRCA1 deficiency. |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
European Commission 305421 |
dc.relation |
Ministerio de Economía y Competitividad SAF2015-64152-R |
dc.relation |
Ministerio de Economía y Competitividad SAF2013-45836-R |
dc.relation |
Ministerio de Economía y Competitividad SAF2012-31881 |
dc.relation |
Ministerio de Economía y Competitividad CB06/07/0023 |
dc.relation |
Ministerio de Economía y Competitividad PIE13/00022 |
dc.relation |
Ministerio de Economía y Competitividad CP10/00617 |
dc.relation |
Ministerio de Economía y Competitividad PI10/01422 |
dc.relation |
Ministerio de Economía y Competitividad PI12/02585 |
dc.relation |
Ministerio de Economía y Competitividad PI13/00285 |
dc.relation |
Ministerio de Economía y Competitividad PI15/00854 |
dc.relation |
Ministerio de Economía y Competitividad PI16/00563 |
dc.relation |
Ministerio de Economía y Competitividad PI16/01218 |
dc.relation |
Ministerio de Economía y Competitividad RD12/0036/0008 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-364 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-338 |
dc.relation |
Nature communications ; Vol. 9 (2018), art. 967 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
dc.subject |
Cancer |
dc.subject |
Double-strand DNA breaks |
dc.subject |
Genomic instability |
dc.subject |
RNA metabolism |
dc.title |
Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1 |
dc.type |
Article |