TY  - JOUR
A1  - Hernández, Gonzalo
A1  - José Ramírez, María
A1  - Minguillón, Jordi
A1  - Quiles, Paco
A1  - Ruiz de Garibay, Gorka
A1  - Aza-Carmona, Miriam
A1  - Bogliolo, Massimo
A1  - Pujol, Roser
A1  - Prados-Carvajal, Rosario
A1  - Fernández, Juana
A1  - García, Nadia
A1  - López, Adrià
A1  - Gutiérrez-Enríquez, Sara
A1  - Diez, Orland
A1  - Benítez, Javier
A1  - Salinas, Mónica
A1  - Teulé, Alex
A1  - Brunet, Joan
A1  - Radice, Paolo
A1  - Peterlongo, Paolo
A1  - Schindler, Detlev
A1  - Huertas, Pablo
A1  - Puente, Xose S.
A1  - Lázaro, Conxi
A1  - Àngel Pujana, Miquel
A1  - Surrallés, Jordi
T1  - Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1
JF  - Nature Communications
N2  - 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.
KW  - cancer
KW  - double-strand DNA breaks
KW  - genomic instability
KW  - RNA metabolism
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319929
VL  - 9
ER  -