Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice

DNA double strand breaks are the most cytotoxic lesions that can occur on the DNA. They can be repaired by different mechanisms and optimal survival requires a tight control between them. Here we uncover protein deneddylation as a major controller of repair pathway choice. Neddylation inhibition cha...

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Autores: Jimeno González, Sonia, Fernández Ávila, María Jesús, Cruz García, Andrés, Cepeda García, Cristina, Gómez Cabello, Daniel, Huertas Sánchez, Pablo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/55953
Acceso en línea:http://hdl.handle.net/11441/55953
https://doi.org/10.1093/nar/gku1384
Access Level:acceso abierto
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spelling Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choiceJimeno González, SoniaFernández Ávila, María JesúsCruz García, AndrésCepeda García, CristinaGómez Cabello, DanielHuertas Sánchez, PabloDNA double strand breaks are the most cytotoxic lesions that can occur on the DNA. They can be repaired by different mechanisms and optimal survival requires a tight control between them. Here we uncover protein deneddylation as a major controller of repair pathway choice. Neddylation inhibition changes the normal repair profile toward an increase on homologous recombination. Indeed, RNF111/UBE2M-mediated neddylation acts as an inhibitor of BRCA1 and CtIP-mediated DNA end resection, a key process in repair pathway choice. By controlling the length of ssDNA produced during DNA resection, protein neddylation not only affects the choice between NHEJ and homologous recombination but also controls the balance between different recombination subpathways. Thus, protein neddylation status has a great impact in the way cells respond to DNA breaks.España , Ministerio de Economía y Competitividad SAF2010-14877Oxford University PressGenéticaMinisterio de Economía y Competitividad (MINECO). España2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/11441/55953https://doi.org/10.1093/nar/gku1384reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésNucleic Acids Research, 43 (2), 987-999.info:eu-repo/grantAgreement/MINECO/SAF2010-14877/http://dx.doi.org/10.1093/nar/gku1384info:eu-repo/semantics/openAccessoai:idus.us.es:11441/559532026-06-17T12:51:07Z
dc.title.none.fl_str_mv Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice
title Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice
spellingShingle Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice
Jimeno González, Sonia
title_short Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice
title_full Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice
title_fullStr Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice
title_full_unstemmed Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice
title_sort Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice
dc.creator.none.fl_str_mv Jimeno González, Sonia
Fernández Ávila, María Jesús
Cruz García, Andrés
Cepeda García, Cristina
Gómez Cabello, Daniel
Huertas Sánchez, Pablo
author Jimeno González, Sonia
author_facet Jimeno González, Sonia
Fernández Ávila, María Jesús
Cruz García, Andrés
Cepeda García, Cristina
Gómez Cabello, Daniel
Huertas Sánchez, Pablo
author_role author
author2 Fernández Ávila, María Jesús
Cruz García, Andrés
Cepeda García, Cristina
Gómez Cabello, Daniel
Huertas Sánchez, Pablo
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Genética
Ministerio de Economía y Competitividad (MINECO). España
description DNA double strand breaks are the most cytotoxic lesions that can occur on the DNA. They can be repaired by different mechanisms and optimal survival requires a tight control between them. Here we uncover protein deneddylation as a major controller of repair pathway choice. Neddylation inhibition changes the normal repair profile toward an increase on homologous recombination. Indeed, RNF111/UBE2M-mediated neddylation acts as an inhibitor of BRCA1 and CtIP-mediated DNA end resection, a key process in repair pathway choice. By controlling the length of ssDNA produced during DNA resection, protein neddylation not only affects the choice between NHEJ and homologous recombination but also controls the balance between different recombination subpathways. Thus, protein neddylation status has a great impact in the way cells respond to DNA breaks.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11441/55953
https://doi.org/10.1093/nar/gku1384
url http://hdl.handle.net/11441/55953
https://doi.org/10.1093/nar/gku1384
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nucleic Acids Research, 43 (2), 987-999.
info:eu-repo/grantAgreement/MINECO/SAF2010-14877/
http://dx.doi.org/10.1093/nar/gku1384
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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