2026-08-29T15:33:52Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/64502025-05-08T07:52:11Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Hernández, Gonzalo
author
Ramírez, María José
author
Minguillón, Jordi
author
Quiles, Paco
author
Ruiz de Garibay, Gorka
author
Aza-Carmona, Miriam
author
Bogliolo, Massimo
author
Pujol, Roser
author
Prados-Carvajal, Rosario
author
Fernández, Juana
author
García, Nadia
author
López, Adrià
author
Gutiérrez-Enríquez, Sara
author
Diez, Orland
author
Benitez, Javier
author
Salinas, Mónica
author
Teulé, Alex
author
Brunet, Joan
author
Radice, Paolo
author
Peterlongo, Paolo
author
Schindler, Detlev
author
Huertas, Pablo
author
Puente, Xose S
author
Lázaro, Conxi
author
Pujana, Miguel Angel
author
Surrallés, Jordi
funder
Institució Catalana de Recerca i Estudis Avançats
funder
Fundación La Marató TV3
funder
Ministerio de Sanidad (España)
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Comisión Europea
funder
Fanconi Anemia Research Fund
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Asociación Española Contra el Cáncer
funder
Government of Catalonia (España)
funder
Instituto de Salud Carlos III
2018-09-24T12:02:02Z
2018-09-24T12:02:02Z
2018
Nat Commun. 2018; 9(1): 967.
10.1038/s41467-018-03433-3
2041-1723
2041-1723
Nature communications
29511213
http://hdl.handle.net/20.500.12105/6450
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.
eng
Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1
research article
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DecappingproteinEDC4_2018.pdf
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DecappingproteinEDC4_2018_MOESM1_ESM(1).pdf
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DecappingproteinEDC4_2018_MOESM2_ESM(1).pdf
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DecappingproteinEDC4_2018.pdf.txt
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DecappingproteinEDC4_2018_MOESM1_ESM(1).pdf.txt
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