RT Journal Article
T1 Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1.
A1 Hernández, Gonzalo
A1 Ramírez, María José
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 Pujana, Miquel Àngel
A1 Surrallés, Jordi
AB 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.
YR 2018
FD 2018-03-06
LK http://hdl.handle.net/10668/12212
UL http://hdl.handle.net/10668/12212
LA en
DS RISalud
RD Apr 7, 2025