The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions

The Cockayne Syndrome Protein B (CSB) plays an essential role in Transcription-Coupled Nucleotide Excision Repair (TC-NER) by recruiting repair proteins once transcription is blocked with a DNA lesion. In fact, CSB-deficient cells are unable to recover from transcription-blocking DNA lesions. 5-Aza-...

ver descrição completa

Detalhes bibliográficos
Autores: Burgos Morón, Estefanía, Calderón Montaño, José Manuel, Pastor Carrillo, Nuria María, Ruiz Castizo, Ángel, Domínguez García, Inmaculada, López Lázaro, Miguel, Mateos Cordero, Santiago, Orta Vázquez, Manuel Luis
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/80521
Acesso em linha:https://hdl.handle.net/11441/80521
https://doi.org/10.18632/oncotarget.26189
Access Level:acceso abierto
Palavra-chave:CSB
5-azadC
DNMT1
DNA damage
transcription
id ES_0171ba0313f731908c545fc7f1584d8a
oai_identifier_str oai:idus.us.es:11441/80521
network_acronym_str ES
network_name_str España
repository_id_str
spelling The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesionsBurgos Morón, EstefaníaCalderón Montaño, José ManuelPastor Carrillo, Nuria MaríaRuiz Castizo, ÁngelDomínguez García, InmaculadaLópez Lázaro, MiguelMateos Cordero, SantiagoOrta Vázquez, Manuel LuisCSB5-azadCDNMT1DNA damagetranscriptionThe Cockayne Syndrome Protein B (CSB) plays an essential role in Transcription-Coupled Nucleotide Excision Repair (TC-NER) by recruiting repair proteins once transcription is blocked with a DNA lesion. In fact, CSB-deficient cells are unable to recover from transcription-blocking DNA lesions. 5-Aza-2′-deoxycytidine (5-azadC) is a nucleoside analogue that covalently traps DNA methyltransferases (DNMTs) onto DNA. This anticancer drug has a double mechanism of action: it reverts aberrant hypermethylation in tumour-suppressor genes, and it induces DNA damage. We have recently reported that Homologous Recombination and XRCC1/PARP play an important role in the repair of 5-azadC-induced DNA damage. However, the mechanisms involved in the repair of the DNMT adducts induced by azadC remain poorly understood. In this paper, we show for the first time the importance of CSB in the repair of azadC-induced DNA lesions. We propose a model in which CSB initiates a signalling pathway to repair transcription blocks induced by incorporated 5-azadC. Indeed, CSB-deficient cells treated with 5-azadC show a delay in the repair of trapped DNMT1, increased levels of DNA damage and reduced survival.España, Fundación Progreso y Salud (PI-0073-2014)Impact JournalsBiología CelularFarmacologíaJunta de Andalucía2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/80521https://doi.org/10.18632/oncotarget.26189reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésPI-0073-2014http://dx.doi.org/10.18632/oncotarget.26189info:eu-repo/semantics/openAccessoai:idus.us.es:11441/805212026-06-17T12:51:07Z
dc.title.none.fl_str_mv The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions
title The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions
spellingShingle The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions
Burgos Morón, Estefanía
CSB
5-azadC
DNMT1
DNA damage
transcription
title_short The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions
title_full The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions
title_fullStr The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions
title_full_unstemmed The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions
title_sort The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions
dc.creator.none.fl_str_mv Burgos Morón, Estefanía
Calderón Montaño, José Manuel
Pastor Carrillo, Nuria María
Ruiz Castizo, Ángel
Domínguez García, Inmaculada
López Lázaro, Miguel
Mateos Cordero, Santiago
Orta Vázquez, Manuel Luis
author Burgos Morón, Estefanía
author_facet Burgos Morón, Estefanía
Calderón Montaño, José Manuel
Pastor Carrillo, Nuria María
Ruiz Castizo, Ángel
Domínguez García, Inmaculada
López Lázaro, Miguel
Mateos Cordero, Santiago
Orta Vázquez, Manuel Luis
author_role author
author2 Calderón Montaño, José Manuel
Pastor Carrillo, Nuria María
Ruiz Castizo, Ángel
Domínguez García, Inmaculada
López Lázaro, Miguel
Mateos Cordero, Santiago
Orta Vázquez, Manuel Luis
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Biología Celular
Farmacología
Junta de Andalucía
dc.subject.none.fl_str_mv CSB
5-azadC
DNMT1
DNA damage
transcription
topic CSB
5-azadC
DNMT1
DNA damage
transcription
description The Cockayne Syndrome Protein B (CSB) plays an essential role in Transcription-Coupled Nucleotide Excision Repair (TC-NER) by recruiting repair proteins once transcription is blocked with a DNA lesion. In fact, CSB-deficient cells are unable to recover from transcription-blocking DNA lesions. 5-Aza-2′-deoxycytidine (5-azadC) is a nucleoside analogue that covalently traps DNA methyltransferases (DNMTs) onto DNA. This anticancer drug has a double mechanism of action: it reverts aberrant hypermethylation in tumour-suppressor genes, and it induces DNA damage. We have recently reported that Homologous Recombination and XRCC1/PARP play an important role in the repair of 5-azadC-induced DNA damage. However, the mechanisms involved in the repair of the DNMT adducts induced by azadC remain poorly understood. In this paper, we show for the first time the importance of CSB in the repair of azadC-induced DNA lesions. We propose a model in which CSB initiates a signalling pathway to repair transcription blocks induced by incorporated 5-azadC. Indeed, CSB-deficient cells treated with 5-azadC show a delay in the repair of trapped DNMT1, increased levels of DNA damage and reduced survival.
publishDate 2018
dc.date.none.fl_str_mv 2018
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/11441/80521
https://doi.org/10.18632/oncotarget.26189
url https://hdl.handle.net/11441/80521
https://doi.org/10.18632/oncotarget.26189
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PI-0073-2014
http://dx.doi.org/10.18632/oncotarget.26189
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 Impact Journals
publisher.none.fl_str_mv Impact Journals
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_ 1869402584020680704
score 15.300719

Registos relacionados