Decapping Protein Edc4 Regulates Dna Repair And Phenocopies Brca1
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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2018 |
| País: | España |
| Recursos: | Universidad de Barcelona |
| Repositório: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/123990 |
| Acesso em linha: | https://hdl.handle.net/2445/123990 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Reparació de l'ADN Càncer Gens DNA repair Cancer Genes |
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Decapping Protein Edc4 Regulates Dna Repair And Phenocopies Brca1Hernández, GonzaloRamírez Bajo, María JoséMinguillón, JordiQuiles, PacoRuiz de Garibay, GorkaAza-Carmona, MiriamBogliolo, MassimoPujol, RoserPrados-Carvajal, RosarioFernandez, JuanaGarcia, NadiaLópez, AdriáGutiérrez Enríquez, SaraDíez Gibert, OrlandBenitez, JavierSalinas Masdeu, MònicaTeulé-Vega, ÀlexBrunet, JoanRadice, PaoloPeterlongo, PaoloSchindler, DetlevHuertas, PabloPuente, Xose S.Lázaro García, ConxiPujana Genestar, M. ÁngelSurrallés, JordiReparació de l'ADNCàncerGensDNA repairCancerGenesBRCA1 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.Nature Publishing Group2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/123990Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41467-018-03433-3Nature Communications, 2018-03-06, Vol. 9https://doi.org/10.1038/s41467-018-03433-3info:eu-repo/grantAgreement/EC/H2020/665919info:eu-repo/grantAgreement/EC/FP7/305421cc-by (c) Hernández, Gonzalo et al., 2018http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1239902026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Decapping Protein Edc4 Regulates Dna Repair And Phenocopies Brca1 |
| title |
Decapping Protein Edc4 Regulates Dna Repair And Phenocopies Brca1 |
| spellingShingle |
Decapping Protein Edc4 Regulates Dna Repair And Phenocopies Brca1 Hernández, Gonzalo Reparació de l'ADN Càncer Gens DNA repair Cancer Genes |
| title_short |
Decapping Protein Edc4 Regulates Dna Repair And Phenocopies Brca1 |
| title_full |
Decapping Protein Edc4 Regulates Dna Repair And Phenocopies Brca1 |
| title_fullStr |
Decapping Protein Edc4 Regulates Dna Repair And Phenocopies Brca1 |
| title_full_unstemmed |
Decapping Protein Edc4 Regulates Dna Repair And Phenocopies Brca1 |
| title_sort |
Decapping Protein Edc4 Regulates Dna Repair And Phenocopies Brca1 |
| dc.creator.none.fl_str_mv |
Hernández, Gonzalo Ramírez Bajo, María José Minguillón, Jordi Quiles, Paco Ruiz de Garibay, Gorka Aza-Carmona, Miriam Bogliolo, Massimo Pujol, Roser Prados-Carvajal, Rosario Fernandez, Juana Garcia, Nadia López, Adriá Gutiérrez Enríquez, Sara Díez Gibert, Orland Benitez, Javier Salinas Masdeu, Mònica Teulé-Vega, Àlex Brunet, Joan Radice, Paolo Peterlongo, Paolo Schindler, Detlev Huertas, Pablo Puente, Xose S. Lázaro García, Conxi Pujana Genestar, M. Ángel Surrallés, Jordi |
| author |
Hernández, Gonzalo |
| author_facet |
Hernández, Gonzalo Ramírez Bajo, María José Minguillón, Jordi Quiles, Paco Ruiz de Garibay, Gorka Aza-Carmona, Miriam Bogliolo, Massimo Pujol, Roser Prados-Carvajal, Rosario Fernandez, Juana Garcia, Nadia López, Adriá Gutiérrez Enríquez, Sara Díez Gibert, Orland Benitez, Javier Salinas Masdeu, Mònica Teulé-Vega, Àlex Brunet, Joan Radice, Paolo Peterlongo, Paolo Schindler, Detlev Huertas, Pablo Puente, Xose S. Lázaro García, Conxi Pujana Genestar, M. Ángel Surrallés, Jordi |
| author_role |
author |
| author2 |
Ramírez Bajo, María José Minguillón, Jordi Quiles, Paco Ruiz de Garibay, Gorka Aza-Carmona, Miriam Bogliolo, Massimo Pujol, Roser Prados-Carvajal, Rosario Fernandez, Juana Garcia, Nadia López, Adriá Gutiérrez Enríquez, Sara Díez Gibert, Orland Benitez, Javier Salinas Masdeu, Mònica Teulé-Vega, Àlex Brunet, Joan Radice, Paolo Peterlongo, Paolo Schindler, Detlev Huertas, Pablo Puente, Xose S. Lázaro García, Conxi Pujana Genestar, M. Ángel Surrallés, Jordi |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Reparació de l'ADN Càncer Gens DNA repair Cancer Genes |
| topic |
Reparació de l'ADN Càncer Gens DNA repair Cancer Genes |
| description |
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. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/123990 |
| url |
https://hdl.handle.net/2445/123990 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1038/s41467-018-03433-3 Nature Communications, 2018-03-06, Vol. 9 https://doi.org/10.1038/s41467-018-03433-3 info:eu-repo/grantAgreement/EC/H2020/665919 info:eu-repo/grantAgreement/EC/FP7/305421 |
| dc.rights.none.fl_str_mv |
cc-by (c) Hernández, Gonzalo et al., 2018 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess |
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cc-by (c) Hernández, Gonzalo et al., 2018 http://creativecommons.org/licenses/by/3.0/es/ |
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openAccess |
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application/pdf |
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Nature Publishing Group |
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Nature Publishing Group |
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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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