Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1
Por:
Hernandez, G, Ramirez, MJ, Minguillon, J, Quiles, P, de Garibay, GR, Aza-Carmona, M, Bogliolo, M, Pujol, R, Prados-Carvajal, R, Fernandez, J, Garcia, N, Lopez, A, Gutierrez-Enriquez, S, Diez, O, Benitez, J, Salinas, M, Teule, A, Brunet, J, Radice, P, Peterlongo, P, Schindler, D, Huertas, P, Puente, XS, Lazaro, C, Pujana, MA, Surralles, J
Publicada:
6 mar 2018
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 recognizes EDC4 with a dual role in decapping and DNA repair whose inactivation phenocopies BRCA1 deficiency.
Filiaciones:
Hernandez, G:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona 08193, Spain
Ramirez, MJ:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona 08193, Spain
Minguillon, J:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona 08193, Spain
Quiles, P:
Bellvitge Inst Biomed Res IDIBELL, Hereditary Canc Programme, Catalan Inst Oncol ICO, Barcelona 08908, Spain
de Garibay, GR:
IDIBELL, ICO, Breast Canc & Syst Biol Lab, Program Canc Therapeut Resistance ProCURE, Barcelona 08908, Spain
Aza-Carmona, M:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona 08193, Spain
Bogliolo, M:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona 08193, Spain
Pujol, R:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona 08193, Spain
Prados-Carvajal, R:
Univ Seville, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, E-41080 Seville, Spain
Univ Seville, Dept Genet, E-41080 Seville, Spain
Fernandez, J:
Bellvitge Inst Biomed Res IDIBELL, Hereditary Canc Programme, Catalan Inst Oncol ICO, Barcelona 08908, Spain
Garcia, N:
IDIBELL, ICO, Breast Canc & Syst Biol Lab, Program Canc Therapeut Resistance ProCURE, Barcelona 08908, Spain
Lopez, A:
Girona Biomed Res Inst IDIBGI, ICO, Hereditary Canc Programme, Girona 17007, Spain
Gutierrez-Enriquez, S:
VHIO, Oncogenet Grp, Barcelona 08035, Spain
Diez, O:
VHIO, Oncogenet Grp, Barcelona 08035, Spain
Hosp Univ Vall dHebron, Area Clin & Mol Genet, Barcelona 08035, Spain
Benitez, J:
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona 08193, Spain
Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Madrid 28029, Spain
Salinas, M:
Bellvitge Inst Biomed Res IDIBELL, Hereditary Canc Programme, Catalan Inst Oncol ICO, Barcelona 08908, Spain
Teule, A:
Bellvitge Inst Biomed Res IDIBELL, Hereditary Canc Programme, Catalan Inst Oncol ICO, Barcelona 08908, Spain
Brunet, J:
Bellvitge Inst Biomed Res IDIBELL, Hereditary Canc Programme, Catalan Inst Oncol ICO, Barcelona 08908, Spain
Girona Biomed Res Inst IDIBGI, ICO, Hereditary Canc Programme, Girona 17007, Spain
Radice, P:
Fdn IRCCS Ist Ricovero & Cura Carattere Sci, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, INT, I-20133 Milan, Italy
Peterlongo, P:
Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, IFOM, Fdn Ist FIRC Oncol Mol, I-20139 Milan, Italy
Unit Mol Bases Genet Risk & Genet Testing, I-20139 Milan, Italy
Schindler, D:
Wurzburg Univ, Dept Human Genet, D-97070 Wurzburg, Germany
Puente, XS:
Univ Oviedo, Dept Biochem & Mol Biol, Inst Univ Oncol, E-33006 Oviedo, Spain
Lazaro, C:
Bellvitge Inst Biomed Res IDIBELL, Hereditary Canc Programme, Catalan Inst Oncol ICO, Barcelona 08908, Spain
Pujana, MA:
IDIBELL, ICO, Breast Canc & Syst Biol Lab, Program Canc Therapeut Resistance ProCURE, Barcelona 08908, Spain
Ctr Invest Biomed Red Oncol CIBERONC, Oviedo 33006, Spain
Surralles, J:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona 08193, Spain
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona 08028, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona 08028, Spain
Gold, Green Published
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