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Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1

Opened Access Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1

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Autor: Hernández, Gonzalo
Ramirez, María José
Minguillón, Jordi
Quiles, Paco
Huertas Sánchez, Pablo
Prados Carvajal, Rosario
Fecha: 2018
Publicado en: Nature Comunications, 9 (967), 1-11.
Tipo de documento: Artículo
Resumen: 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...
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Cita: Hernández, G., Ramirez, M.J., Minguillón, J., Quiles, P., Huertas Sánchez, P. y Prados Carvajal, R. (2018). Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1. Nature Comunications, 9 (967), 1-11.
Tamaño: 1.843Mb
Formato: PDF

URI: https://hdl.handle.net/11441/70991

DOI: 10.1038/s41467-018-03433-3

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