RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised

Autores
Choudhary, Ramveer; Muñoz, Juan Cristóbal; Beckerman, Inés; Bastianello, Giulia; Bouvier, León Alberto; Foiani, Marco; Muñoz, Manuel Javier
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In response to DNA damage, RPB1, the catalytic subunit of RNA Polymerase II (RNAPII), is degraded by the ubiquitin-proteasome system. Degradation models only consider transcriptionally engaged molecules, where a stalled RNAPII complex functions as a lesion recognition factor and its RPB1 subunit is proposed to be subsequently degraded to facilitate access of core Nucleotide Excision Repair (NER) factors. This Transcription Coupled repair is complemented by the Global Genome repair (GG-NER) system, where lesions are recognized by the XPE and XPC factors. Here we show that RPB1 degradation is controlled in trans by a pathway that depends on NER activity, irrespectively of whether the lesion is recognized by RNAPII itself or by GG-NER factors. Incomplete lesion repair due to absence of any core NER factor enhances RPB1 degradation, indicating that the signal controlling RPB1 abundance is started by lesion recognition and continues until DNA repair is completed. Consistent with an in trans mechanism, damage-induced RPB1 degradation is not restricted to active nor phosphorylated RPB1 molecules and depends on Cullin-RING ubiquitin ligases. These findings uncover a repair-dependent mechanism controlling RPB1 levels and provide a rationale for the control of gene expression under stress, where more damage implies more repair and less RPB1 levels, hence restricting RNAPII activity.
Fil: Choudhary, Ramveer. Università degli Studi di Milano; Italia
Fil: Muñoz, Juan Cristóbal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Beckerman, Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Bastianello, Giulia. Università degli Studi di Milano; Italia
Fil: Bouvier, León Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Foiani, Marco. Università degli Studi di Milano; Italia
Fil: Muñoz, Manuel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Materia
DNA DAMAGE
NER
RNAPII
UV IRRADIATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/276403
Acceder
id CONICETDig_5dee8083b03c50af780ab2ff9735591f
oai_identifier_str oai:ri.conicet.gov.ar:11336/276403
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is RecognisedChoudhary, RamveerMuñoz, Juan CristóbalBeckerman, InésBastianello, GiuliaBouvier, León AlbertoFoiani, MarcoMuñoz, Manuel JavierDNA DAMAGENERRNAPIIUV IRRADIATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In response to DNA damage, RPB1, the catalytic subunit of RNA Polymerase II (RNAPII), is degraded by the ubiquitin-proteasome system. Degradation models only consider transcriptionally engaged molecules, where a stalled RNAPII complex functions as a lesion recognition factor and its RPB1 subunit is proposed to be subsequently degraded to facilitate access of core Nucleotide Excision Repair (NER) factors. This Transcription Coupled repair is complemented by the Global Genome repair (GG-NER) system, where lesions are recognized by the XPE and XPC factors. Here we show that RPB1 degradation is controlled in trans by a pathway that depends on NER activity, irrespectively of whether the lesion is recognized by RNAPII itself or by GG-NER factors. Incomplete lesion repair due to absence of any core NER factor enhances RPB1 degradation, indicating that the signal controlling RPB1 abundance is started by lesion recognition and continues until DNA repair is completed. Consistent with an in trans mechanism, damage-induced RPB1 degradation is not restricted to active nor phosphorylated RPB1 molecules and depends on Cullin-RING ubiquitin ligases. These findings uncover a repair-dependent mechanism controlling RPB1 levels and provide a rationale for the control of gene expression under stress, where more damage implies more repair and less RPB1 levels, hence restricting RNAPII activity.Fil: Choudhary, Ramveer. Università degli Studi di Milano; ItaliaFil: Muñoz, Juan Cristóbal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Beckerman, Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Bastianello, Giulia. Università degli Studi di Milano; ItaliaFil: Bouvier, León Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Foiani, Marco. Università degli Studi di Milano; ItaliaFil: Muñoz, Manuel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaCold Spring Harbor Laboratory Press2024-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/276403Choudhary, Ramveer; Muñoz, Juan Cristóbal; Beckerman, Inés; Bastianello, Giulia; Bouvier, León Alberto; et al.; RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised; Cold Spring Harbor Laboratory Press; Biorxiv; 8-2024; 1-432692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2024.08.30.610509v1.article-infoinfo:eu-repo/semantics/altIdentifier/doi/10.1101/2024.08.30.610509info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-03T10:00:31Zoai:ri.conicet.gov.ar:11336/276403instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-12-03 10:00:31.668CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised
title RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised
spellingShingle RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised
Choudhary, Ramveer
DNA DAMAGE
NER
RNAPII
UV IRRADIATION
title_short RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised
title_full RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised
title_fullStr RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised
title_full_unstemmed RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised
title_sort RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised
dc.creator.none.fl_str_mv Choudhary, Ramveer
Muñoz, Juan Cristóbal
Beckerman, Inés
Bastianello, Giulia
Bouvier, León Alberto
Foiani, Marco
Muñoz, Manuel Javier
author Choudhary, Ramveer
author_facet Choudhary, Ramveer
Muñoz, Juan Cristóbal
Beckerman, Inés
Bastianello, Giulia
Bouvier, León Alberto
Foiani, Marco
Muñoz, Manuel Javier
author_role author
author2 Muñoz, Juan Cristóbal
Beckerman, Inés
Bastianello, Giulia
Bouvier, León Alberto
Foiani, Marco
Muñoz, Manuel Javier
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv DNA DAMAGE
NER
RNAPII
UV IRRADIATION
topic DNA DAMAGE
NER
RNAPII
UV IRRADIATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In response to DNA damage, RPB1, the catalytic subunit of RNA Polymerase II (RNAPII), is degraded by the ubiquitin-proteasome system. Degradation models only consider transcriptionally engaged molecules, where a stalled RNAPII complex functions as a lesion recognition factor and its RPB1 subunit is proposed to be subsequently degraded to facilitate access of core Nucleotide Excision Repair (NER) factors. This Transcription Coupled repair is complemented by the Global Genome repair (GG-NER) system, where lesions are recognized by the XPE and XPC factors. Here we show that RPB1 degradation is controlled in trans by a pathway that depends on NER activity, irrespectively of whether the lesion is recognized by RNAPII itself or by GG-NER factors. Incomplete lesion repair due to absence of any core NER factor enhances RPB1 degradation, indicating that the signal controlling RPB1 abundance is started by lesion recognition and continues until DNA repair is completed. Consistent with an in trans mechanism, damage-induced RPB1 degradation is not restricted to active nor phosphorylated RPB1 molecules and depends on Cullin-RING ubiquitin ligases. These findings uncover a repair-dependent mechanism controlling RPB1 levels and provide a rationale for the control of gene expression under stress, where more damage implies more repair and less RPB1 levels, hence restricting RNAPII activity.
Fil: Choudhary, Ramveer. Università degli Studi di Milano; Italia
Fil: Muñoz, Juan Cristóbal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Beckerman, Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Bastianello, Giulia. Università degli Studi di Milano; Italia
Fil: Bouvier, León Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Foiani, Marco. Università degli Studi di Milano; Italia
Fil: Muñoz, Manuel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
description In response to DNA damage, RPB1, the catalytic subunit of RNA Polymerase II (RNAPII), is degraded by the ubiquitin-proteasome system. Degradation models only consider transcriptionally engaged molecules, where a stalled RNAPII complex functions as a lesion recognition factor and its RPB1 subunit is proposed to be subsequently degraded to facilitate access of core Nucleotide Excision Repair (NER) factors. This Transcription Coupled repair is complemented by the Global Genome repair (GG-NER) system, where lesions are recognized by the XPE and XPC factors. Here we show that RPB1 degradation is controlled in trans by a pathway that depends on NER activity, irrespectively of whether the lesion is recognized by RNAPII itself or by GG-NER factors. Incomplete lesion repair due to absence of any core NER factor enhances RPB1 degradation, indicating that the signal controlling RPB1 abundance is started by lesion recognition and continues until DNA repair is completed. Consistent with an in trans mechanism, damage-induced RPB1 degradation is not restricted to active nor phosphorylated RPB1 molecules and depends on Cullin-RING ubiquitin ligases. These findings uncover a repair-dependent mechanism controlling RPB1 levels and provide a rationale for the control of gene expression under stress, where more damage implies more repair and less RPB1 levels, hence restricting RNAPII activity.
publishDate 2024
dc.date.none.fl_str_mv 2024-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/276403
Choudhary, Ramveer; Muñoz, Juan Cristóbal; Beckerman, Inés; Bastianello, Giulia; Bouvier, León Alberto; et al.; RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised; Cold Spring Harbor Laboratory Press; Biorxiv; 8-2024; 1-43
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/276403
identifier_str_mv Choudhary, Ramveer; Muñoz, Juan Cristóbal; Beckerman, Inés; Bastianello, Giulia; Bouvier, León Alberto; et al.; RNA Polymerase II Degradation Triggered by DNA Repair Occurs In Trans and Independently of how the Lesion is Recognised; Cold Spring Harbor Laboratory Press; Biorxiv; 8-2024; 1-43
2692-8205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2024.08.30.610509v1.article-info
info:eu-repo/semantics/altIdentifier/doi/10.1101/2024.08.30.610509
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1850505987912368128
score 13.214268

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