Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1

Gonzalo Hernández; María José Ramírez; Jordi Minguillón; Paco Quiles; Gorka Ruiz De Garibay; Miriam Aza-Carmona; Massimo Bogliolo; Roser Pujol; Rosario Prados-Carvajal; Juana Fernández; Nadia García; Adrià López; Sara Gutiérrez-Enríquez; Orland Diez; Javier Benítez; Mónica Salinas; Alex Teulé; Joan Brunet; Paolo Radice; Paolo Peterlongo; Detlev Schindler; Pablo Huertas; Xose S. Puente; Conxi Lázaro; Miquel Àngel Pujana; Jordi Surrallés; Jordi Minguillon Pedreño

doi:https://doi.org/10.1038/s41467-018-03433-3

Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1

Gonzalo Hernández, María José Ramírez, Jordi Minguillón, Paco Quiles, Gorka Ruiz De Garibay, Miriam Aza-Carmona, Massimo Bogliolo, Roser Pujol, Rosario Prados-Carvajal, Juana Fernández, Nadia García, Adrià López, Sara Gutiérrez-Enríquez, Orland Diez, Javier Benítez, Mónica Salinas, Alex Teulé, Joan Brunet, Paolo Radice, Paolo PeterlongoDetlev Schindler, Pablo Huertas, Xose S. Puente, Conxi Lázaro, Miquel Àngel Pujana, Jordi Surrallés, Jordi Minguillon Pedreño

Department of Genetics and Microbiology

Research output: Contribution to journal › Article › Research

29 Citations (Scopus)

Abstract

© 2018 The Author(s). 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.

Original language	English
Article number	967
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-03433-3
Publication status	Published - 1 Dec 2018

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Hernández, G., Ramírez, M. J., Minguillón, J., Quiles, P., Ruiz De Garibay, G., Aza-Carmona, M., Bogliolo, M., Pujol, R., Prados-Carvajal, R., Fernández, J., García, N., López, A., Gutiérrez-Enríquez, S., Diez, O., Benítez, J., Salinas, M., Teulé, A., Brunet, J., Radice, P., ... Minguillon Pedreño, J. (2018). Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1. Nature Communications, 9, [967]. https://doi.org/10.1038/s41467-018-03433-3

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title = "Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1",

abstract = "{\textcopyright} 2018 The Author(s). 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.",

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Hernández, G, Ramírez, MJ, Minguillón, J, Quiles, P, Ruiz De Garibay, G, Aza-Carmona, M, Bogliolo, M, Pujol, R, Prados-Carvajal, R, Fernández, J, García, N, López, A, Gutiérrez-Enríquez, S, Diez, O, Benítez, J, Salinas, M, Teulé, A, Brunet, J, Radice, P, Peterlongo, P, Schindler, D, Huertas, P, Puente, XS, Lázaro, C, Pujana, MÀ, Surrallés, J & Minguillon Pedreño, J 2018, 'Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1', Nature Communications, vol. 9, 967. https://doi.org/10.1038/s41467-018-03433-3

TY - JOUR

T1 - Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1

AU - Hernández, Gonzalo

AU - Ramírez, María José

AU - Minguillón, Jordi

AU - Quiles, Paco

AU - Ruiz De Garibay, Gorka

AU - Aza-Carmona, Miriam

AU - Bogliolo, Massimo

AU - Pujol, Roser

AU - Prados-Carvajal, Rosario

AU - Fernández, Juana

AU - García, Nadia

AU - López, Adrià

AU - Gutiérrez-Enríquez, Sara

AU - Diez, Orland

AU - Benítez, Javier

AU - Salinas, Mónica

AU - Teulé, Alex

AU - Brunet, Joan

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Schindler, Detlev

AU - Huertas, Pablo

AU - Puente, Xose S.

AU - Lázaro, Conxi

AU - Pujana, Miquel Àngel

AU - Surrallés, Jordi

AU - Minguillon Pedreño, Jordi

PY - 2018/12/1

Y1 - 2018/12/1

N2 - © 2018 The Author(s). 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.

AB - © 2018 The Author(s). 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.

U2 - https://doi.org/10.1038/s41467-018-03433-3

DO - https://doi.org/10.1038/s41467-018-03433-3

M3 - Article

C2 - 29511213

VL - 9

M1 - 967

ER -

Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1

Abstract

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