CtIP-mediated Alternative mRNA Splicing Fine-tunes the DNA Damage Response

In order to survive to the exposure of DNA damaging agents, cells activate a complex response that coordinates the cellular metabolism, cell cycle progression, and DNA repair. Among many other events, recent evidence has described global changes in mRNA splicing in cells treated with genotoxic agent...

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Detalles Bibliográficos
Autores: Prados Carvajal, Rosario, Rodríguez Real, Guillermo, Gutiérrez Pozo, Gabriel, Huertas Sánchez, Pablo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/141084
Acceso en línea:https://hdl.handle.net/11441/141084
https://doi.org/10.1261/rna.078519.120
Access Level:acceso abierto
Palabra clave:CtIP
DNA damage response
MRNA splicing
PIF1
SF3B complex
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spelling CtIP-mediated Alternative mRNA Splicing Fine-tunes the DNA Damage ResponsePrados Carvajal, RosarioRodríguez Real, GuillermoGutiérrez Pozo, GabrielHuertas Sánchez, PabloCtIPDNA damage responseMRNA splicingPIF1SF3B complexIn order to survive to the exposure of DNA damaging agents, cells activate a complex response that coordinates the cellular metabolism, cell cycle progression, and DNA repair. Among many other events, recent evidence has described global changes in mRNA splicing in cells treated with genotoxic agents. Here, we explore further this DNA damage-dependent alternative splicing. Indeed, we show that both the splicing factor SF3B2 and the repair protein CtIP contribute to the global pattern of splicing both in cells treated or not to DNA damaging agents. Additionally, we focus on a specific DNA damage- and CtIP-dependent alternative splicing event of the helicase PIF1 and explore its relevance for the survival of cells upon exposure to ionizing radiation. Indeed, we describe how the nuclear, active form of PIF1 is substituted by a splicing variant, named vPIF1, in a fashion that requires both the presence of DNA damage and CtIP. Interestingly, timely expression of vPIF1 is required for optimal survival to exposure to DNA damaging agents, but early expression of this isoform delays early events of the DNA damage response. On the contrary, expression of the full length PIF1 facilitates those early events but increases the sensitivity to DNA damaging agents if the expression is maintained long-term.Ministerio de Economía y Competitividad SAF2016-74855-PCold Spring Harbor Laboratory PressGenéticaMinisterio de Economía y Competitividad (MINECO). España2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/141084https://doi.org/10.1261/rna.078519.120reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésRNA, 27 (3), 303-323.SAF2016-74855-Phttp://doi.org/10.1261/rna.078519.120info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1410842026-06-17T12:51:07Z
dc.title.none.fl_str_mv CtIP-mediated Alternative mRNA Splicing Fine-tunes the DNA Damage Response
title CtIP-mediated Alternative mRNA Splicing Fine-tunes the DNA Damage Response
spellingShingle CtIP-mediated Alternative mRNA Splicing Fine-tunes the DNA Damage Response
Prados Carvajal, Rosario
CtIP
DNA damage response
MRNA splicing
PIF1
SF3B complex
title_short CtIP-mediated Alternative mRNA Splicing Fine-tunes the DNA Damage Response
title_full CtIP-mediated Alternative mRNA Splicing Fine-tunes the DNA Damage Response
title_fullStr CtIP-mediated Alternative mRNA Splicing Fine-tunes the DNA Damage Response
title_full_unstemmed CtIP-mediated Alternative mRNA Splicing Fine-tunes the DNA Damage Response
title_sort CtIP-mediated Alternative mRNA Splicing Fine-tunes the DNA Damage Response
dc.creator.none.fl_str_mv Prados Carvajal, Rosario
Rodríguez Real, Guillermo
Gutiérrez Pozo, Gabriel
Huertas Sánchez, Pablo
author Prados Carvajal, Rosario
author_facet Prados Carvajal, Rosario
Rodríguez Real, Guillermo
Gutiérrez Pozo, Gabriel
Huertas Sánchez, Pablo
author_role author
author2 Rodríguez Real, Guillermo
Gutiérrez Pozo, Gabriel
Huertas Sánchez, Pablo
author2_role 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 damage response
MRNA splicing
PIF1
SF3B complex
topic CtIP
DNA damage response
MRNA splicing
PIF1
SF3B complex
description In order to survive to the exposure of DNA damaging agents, cells activate a complex response that coordinates the cellular metabolism, cell cycle progression, and DNA repair. Among many other events, recent evidence has described global changes in mRNA splicing in cells treated with genotoxic agents. Here, we explore further this DNA damage-dependent alternative splicing. Indeed, we show that both the splicing factor SF3B2 and the repair protein CtIP contribute to the global pattern of splicing both in cells treated or not to DNA damaging agents. Additionally, we focus on a specific DNA damage- and CtIP-dependent alternative splicing event of the helicase PIF1 and explore its relevance for the survival of cells upon exposure to ionizing radiation. Indeed, we describe how the nuclear, active form of PIF1 is substituted by a splicing variant, named vPIF1, in a fashion that requires both the presence of DNA damage and CtIP. Interestingly, timely expression of vPIF1 is required for optimal survival to exposure to DNA damaging agents, but early expression of this isoform delays early events of the DNA damage response. On the contrary, expression of the full length PIF1 facilitates those early events but increases the sensitivity to DNA damaging agents if the expression is maintained long-term.
publishDate 2021
dc.date.none.fl_str_mv 2021
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 https://hdl.handle.net/11441/141084
https://doi.org/10.1261/rna.078519.120
url https://hdl.handle.net/11441/141084
https://doi.org/10.1261/rna.078519.120
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv RNA, 27 (3), 303-323.
SAF2016-74855-P
http://doi.org/10.1261/rna.078519.120
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 Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory 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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