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 recurso: | artículo |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:188030 |
| Acceso en línea: | https://ddd.uab.cat/record/188030 https://dx.doi.org/urn:doi:10.1038/s41467-018-03433-3 |
| Access Level: | acceso abierto |
| Palabra clave: | Cancer Double-strand DNA breaks Genomic instability RNA metabolism |
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oai:ddd.uab.cat:188030 |
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España |
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| 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 Viedma, Gonzalo|||0000-0002-3048-9607 Cancer Double-strand DNA breaks Genomic instability RNA metabolism |
| 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 Viedma, Gonzalo|||0000-0002-3048-9607 Ramírez de Haro, Ma. José|||0000-0003-1417-7731 Minguillón Pedreño, Jordi|||0000-0003-2124-8294 Quiles, Francisco Ruiz de Garibay, G. Aza-Carmona, Miriam|||0000-0003-4448-9541 Bogliolo, Massimo|||0000-0001-8240-7784 Pujol Calvet, Maria Roser|||0000-0003-1840-5455 Prados-Carvajal, Rosario Fernández-Rodríguez, Juana García, Nadia López, Adrià Gutiérrez-Enríquez, Sara|||0000-0002-1711-6101 Diez, Orland|||0000-0001-7339-0570 Benitez, Javier|||0000-0002-0923-7202 Salinas, Monica Teule, Alex|||0000-0003-0028-7200 Brunet, Joan|||0000-0003-1945-3512 Radice, Paolo|||0000-0001-6298-4111 Peterlongo, Paolo|||0000-0001-6951-6855 Schindler, Detlev Huertas, Pablo Puente, Xose P. Lázaro, Coxi Pujana, Miguel Angel|||0000-0003-3222-4044 Surralles, Jordi|||0000-0002-4041-7519 |
| author |
Hernández Viedma, Gonzalo|||0000-0002-3048-9607 |
| author_facet |
Hernández Viedma, Gonzalo|||0000-0002-3048-9607 Ramírez de Haro, Ma. José|||0000-0003-1417-7731 Minguillón Pedreño, Jordi|||0000-0003-2124-8294 Quiles, Francisco Ruiz de Garibay, G. Aza-Carmona, Miriam|||0000-0003-4448-9541 Bogliolo, Massimo|||0000-0001-8240-7784 Pujol Calvet, Maria Roser|||0000-0003-1840-5455 Prados-Carvajal, Rosario Fernández-Rodríguez, Juana García, Nadia López, Adrià Gutiérrez-Enríquez, Sara|||0000-0002-1711-6101 Diez, Orland|||0000-0001-7339-0570 Benitez, Javier|||0000-0002-0923-7202 Salinas, Monica Teule, Alex|||0000-0003-0028-7200 Brunet, Joan|||0000-0003-1945-3512 Radice, Paolo|||0000-0001-6298-4111 Peterlongo, Paolo|||0000-0001-6951-6855 Schindler, Detlev Huertas, Pablo Puente, Xose P. Lázaro, Coxi Pujana, Miguel Angel|||0000-0003-3222-4044 Surralles, Jordi|||0000-0002-4041-7519 |
| author_role |
author |
| author2 |
Ramírez de Haro, Ma. José|||0000-0003-1417-7731 Minguillón Pedreño, Jordi|||0000-0003-2124-8294 Quiles, Francisco Ruiz de Garibay, G. Aza-Carmona, Miriam|||0000-0003-4448-9541 Bogliolo, Massimo|||0000-0001-8240-7784 Pujol Calvet, Maria Roser|||0000-0003-1840-5455 Prados-Carvajal, Rosario Fernández-Rodríguez, Juana García, Nadia López, Adrià Gutiérrez-Enríquez, Sara|||0000-0002-1711-6101 Diez, Orland|||0000-0001-7339-0570 Benitez, Javier|||0000-0002-0923-7202 Salinas, Monica Teule, Alex|||0000-0003-0028-7200 Brunet, Joan|||0000-0003-1945-3512 Radice, Paolo|||0000-0001-6298-4111 Peterlongo, Paolo|||0000-0001-6951-6855 Schindler, Detlev Huertas, Pablo Puente, Xose P. Lázaro, Coxi Pujana, Miguel Angel|||0000-0003-3222-4044 Surralles, Jordi|||0000-0002-4041-7519 |
| 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 |
Cancer Double-strand DNA breaks Genomic instability RNA metabolism |
| topic |
Cancer Double-strand DNA breaks Genomic instability RNA metabolism |
| 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 |
2 2018-01-01 2018 2018-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/188030 https://dx.doi.org/urn:doi:10.1038/s41467-018-03433-3 |
| url |
https://ddd.uab.cat/record/188030 https://dx.doi.org/urn:doi:10.1038/s41467-018-03433-3 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
European Commission https://doi.org/10.13039/501100000780 305421 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-64152-R Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-45836-R Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2012-31881 Ministerio de Sanidad y Consumo https://doi.org/10.13039/501100003329 CB06/07/0023 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PIE13/00022 Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 CP10/00617 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI10/01422 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/02585 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/00285 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/00854 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/00563 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/01218 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0036/0008 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-364 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-338 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1Hernández Viedma, Gonzalo|||0000-0002-3048-9607Ramírez de Haro, Ma. José|||0000-0003-1417-7731Minguillón Pedreño, Jordi|||0000-0003-2124-8294Quiles, FranciscoRuiz de Garibay, G.Aza-Carmona, Miriam|||0000-0003-4448-9541Bogliolo, Massimo|||0000-0001-8240-7784Pujol Calvet, Maria Roser|||0000-0003-1840-5455Prados-Carvajal, RosarioFernández-Rodríguez, JuanaGarcía, NadiaLópez, AdriàGutiérrez-Enríquez, Sara|||0000-0002-1711-6101Diez, Orland|||0000-0001-7339-0570Benitez, Javier|||0000-0002-0923-7202Salinas, MonicaTeule, Alex|||0000-0003-0028-7200Brunet, Joan|||0000-0003-1945-3512Radice, Paolo|||0000-0001-6298-4111Peterlongo, Paolo|||0000-0001-6951-6855Schindler, DetlevHuertas, PabloPuente, Xose P.Lázaro, CoxiPujana, Miguel Angel|||0000-0003-3222-4044Surralles, Jordi|||0000-0002-4041-7519CancerDouble-strand DNA breaksGenomic instabilityRNA metabolismBRCA1 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. 22018-01-0120182018-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/188030https://dx.doi.org/urn:doi:10.1038/s41467-018-03433-3reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengEuropean Commission https://doi.org/10.13039/501100000780 305421Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-64152-RMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-45836-RMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2012-31881Ministerio de Sanidad y Consumo https://doi.org/10.13039/501100003329 CB06/07/0023Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PIE13/00022Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 CP10/00617Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI10/01422Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/02585Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/00285Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/00854Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/00563Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/01218Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0036/0008Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-364Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-338open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1880302026-06-06T12:50:31Z |
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15,301603 |