Multiple Roles of the Splicing Complex SF3B in DNA end Resection and Homologous Recombination

The appropriate repair of DNA double strand breaks is critical for genome maintenance. Thus, several cellular pathways collaborate to orchestrate a coordinated response. These include the repair of the breaks, which could be achieved by different mechanisms. A key protein involved in the regulation...

Descripción completa

Detalles Bibliográficos
Autores: López Saavedra, Ana, Prados Carvajal, Rosario, Cepeda García, Cristina, Jimeno González, Sonia, Huertas Sánchez, Pablo
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/166631
Acceso en línea:https://hdl.handle.net/11441/166631
https://doi.org/10.1016/j.dnarep.2018.04.003
Access Level:acceso abierto
Palabra clave:CtIP
DNA resection
Homologous recombination
RNA splicing
SF3B
id ES_fb149a9201a25fc2e635dedc26bbd739
oai_identifier_str oai:idus.us.es:11441/166631
network_acronym_str ES
network_name_str España
repository_id_str
spelling Multiple Roles of the Splicing Complex SF3B in DNA end Resection and Homologous RecombinationLópez Saavedra, AnaPrados Carvajal, RosarioCepeda García, CristinaJimeno González, SoniaHuertas Sánchez, PabloCtIPDNA resectionHomologous recombinationRNA splicingSF3BThe appropriate repair of DNA double strand breaks is critical for genome maintenance. Thus, several cellular pathways collaborate to orchestrate a coordinated response. These include the repair of the breaks, which could be achieved by different mechanisms. A key protein involved in the regulation of the repair of broken chromosomes is CtIP. Here, we have found new partners of CtIP involved in the regulation of DNA break repair through affecting DNA end resection. We focus on the splicing complex SF3B and show that its depletion impairs DNA end resection and hampers homologous recombination. Functionally, SF3B controls CtIP function at, as least, two levels: by affecting CtIP mRNA levels and controlling CtIP recruitment to DNA breaks, in a way that requires ATM-mediated phosphorylation of SF3B2 at serine 289. Indeed, overexpression of CtIP rescues the resection defect caused by SF3B downregulation. Strikingly, other SF3B depletion phenotypes, such as impaired homologous recombination or cellular sensitivity to DNA damaging agents, are independent of CtIP levels, suggesting a more general role of SF3B in controlling the response to chromosome breaks.Ministerio de Economía y Competitividad SAF2013-43255-PElsevierGenéticaMinisterio de Economía y Competitividad (MINECO). España2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/166631https://doi.org/10.1016/j.dnarep.2018.04.003reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésDNA Repair, 66-67, 11-23.SAF2013-43255-Phttps://doi.org/10.1016/j.dnarep.2018.04.003info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1666312026-06-17T12:51:07Z
dc.title.none.fl_str_mv Multiple Roles of the Splicing Complex SF3B in DNA end Resection and Homologous Recombination
title Multiple Roles of the Splicing Complex SF3B in DNA end Resection and Homologous Recombination
spellingShingle Multiple Roles of the Splicing Complex SF3B in DNA end Resection and Homologous Recombination
López Saavedra, Ana
CtIP
DNA resection
Homologous recombination
RNA splicing
SF3B
title_short Multiple Roles of the Splicing Complex SF3B in DNA end Resection and Homologous Recombination
title_full Multiple Roles of the Splicing Complex SF3B in DNA end Resection and Homologous Recombination
title_fullStr Multiple Roles of the Splicing Complex SF3B in DNA end Resection and Homologous Recombination
title_full_unstemmed Multiple Roles of the Splicing Complex SF3B in DNA end Resection and Homologous Recombination
title_sort Multiple Roles of the Splicing Complex SF3B in DNA end Resection and Homologous Recombination
dc.creator.none.fl_str_mv López Saavedra, Ana
Prados Carvajal, Rosario
Cepeda García, Cristina
Jimeno González, Sonia
Huertas Sánchez, Pablo
author López Saavedra, Ana
author_facet López Saavedra, Ana
Prados Carvajal, Rosario
Cepeda García, Cristina
Jimeno González, Sonia
Huertas Sánchez, Pablo
author_role author
author2 Prados Carvajal, Rosario
Cepeda García, Cristina
Jimeno González, Sonia
Huertas Sánchez, Pablo
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Genética
Ministerio de Economía y Competitividad (MINECO). España
dc.subject.none.fl_str_mv CtIP
DNA resection
Homologous recombination
RNA splicing
SF3B
topic CtIP
DNA resection
Homologous recombination
RNA splicing
SF3B
description The appropriate repair of DNA double strand breaks is critical for genome maintenance. Thus, several cellular pathways collaborate to orchestrate a coordinated response. These include the repair of the breaks, which could be achieved by different mechanisms. A key protein involved in the regulation of the repair of broken chromosomes is CtIP. Here, we have found new partners of CtIP involved in the regulation of DNA break repair through affecting DNA end resection. We focus on the splicing complex SF3B and show that its depletion impairs DNA end resection and hampers homologous recombination. Functionally, SF3B controls CtIP function at, as least, two levels: by affecting CtIP mRNA levels and controlling CtIP recruitment to DNA breaks, in a way that requires ATM-mediated phosphorylation of SF3B2 at serine 289. Indeed, overexpression of CtIP rescues the resection defect caused by SF3B downregulation. Strikingly, other SF3B depletion phenotypes, such as impaired homologous recombination or cellular sensitivity to DNA damaging agents, are independent of CtIP levels, suggesting a more general role of SF3B in controlling the response to chromosome breaks.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/166631
https://doi.org/10.1016/j.dnarep.2018.04.003
url https://hdl.handle.net/11441/166631
https://doi.org/10.1016/j.dnarep.2018.04.003
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv DNA Repair, 66-67, 11-23.
SAF2013-43255-P
https://doi.org/10.1016/j.dnarep.2018.04.003
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 Elsevier
publisher.none.fl_str_mv Elsevier
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
_version_ 1869425296452616192
score 15.81155

Similares en LA Referencia