2026-05-22T00:05:13Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/64502025-05-08T07:52:11Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2018 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. 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 Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1