Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain

Autores
Bedez, Claire; Lotz, Christophe; Batisse, Claire; Broeck, Arnaud Vanden; Stote, Roland H.; Howard, Eduardo Ignacio; Pradeau-Aubreton, Karine; Ruff, Marc; Lamour, Valérie
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Type 2 DNA topoisomerases (Top2) are critical components of key protein complexes involved in DNA replication, chromosome condensation and segregation, as well as gene transcription. The Top2 were found to be the main targets of anticancer agents, leading to intensive efforts to understand their functional and physiological role as well as their molecular structure. Post-translational modifications have been reported to influence Top2 enzyme activities in particular those of the mammalian Top2α isoform. In this study, we identified phosphorylation, and for the first time, acetylation sites in the human Top2α isoform produced in eukaryotic expression systems. Structural analysis revealed that acetylation sites are clustered on the catalytic domains of the homodimer while phosphorylation sites are located in the C-terminal domain responsible for nuclear localization. Biochemical analysis of the eukaryotic-specific K168 residue in the ATPase domain shows that acetylation affects a key position regulating ATP hydrolysis through the modulation of dimerization. Our findings suggest that acetylation of specific sites involved in the allosteric regulation of human Top2 may provide a mechanism for modulation of its catalytic activity.
Fil: Bedez, Claire. Université de Strasbourg; Francia
Fil: Lotz, Christophe. Université de Strasbourg; Francia
Fil: Batisse, Claire. Université de Strasbourg; Francia
Fil: Broeck, Arnaud Vanden. Université de Strasbourg; Francia
Fil: Stote, Roland H.. Université de Strasbourg; Francia
Fil: Howard, Eduardo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina
Fil: Pradeau-Aubreton, Karine. Université de Strasbourg; Francia
Fil: Ruff, Marc. Université de Strasbourg; Francia
Fil: Lamour, Valérie. Université de Strasbourg; Francia
Materia
DNA TOPOISOMERASE 2α
POST-TRANSLATIONAL MODIFICATIONS
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:11336/89288
Acceder
id CONICETDig_c0e2e73594a5f713f06064a3d605afc1
oai_identifier_str oai:ri.conicet.gov.ar:11336/89288
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domainBedez, ClaireLotz, ChristopheBatisse, ClaireBroeck, Arnaud VandenStote, Roland H.Howard, Eduardo IgnacioPradeau-Aubreton, KarineRuff, MarcLamour, ValérieDNA TOPOISOMERASE 2αPOST-TRANSLATIONAL MODIFICATIONShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Type 2 DNA topoisomerases (Top2) are critical components of key protein complexes involved in DNA replication, chromosome condensation and segregation, as well as gene transcription. The Top2 were found to be the main targets of anticancer agents, leading to intensive efforts to understand their functional and physiological role as well as their molecular structure. Post-translational modifications have been reported to influence Top2 enzyme activities in particular those of the mammalian Top2α isoform. In this study, we identified phosphorylation, and for the first time, acetylation sites in the human Top2α isoform produced in eukaryotic expression systems. Structural analysis revealed that acetylation sites are clustered on the catalytic domains of the homodimer while phosphorylation sites are located in the C-terminal domain responsible for nuclear localization. Biochemical analysis of the eukaryotic-specific K168 residue in the ATPase domain shows that acetylation affects a key position regulating ATP hydrolysis through the modulation of dimerization. Our findings suggest that acetylation of specific sites involved in the allosteric regulation of human Top2 may provide a mechanism for modulation of its catalytic activity.Fil: Bedez, Claire. Université de Strasbourg; FranciaFil: Lotz, Christophe. Université de Strasbourg; FranciaFil: Batisse, Claire. Université de Strasbourg; FranciaFil: Broeck, Arnaud Vanden. Université de Strasbourg; FranciaFil: Stote, Roland H.. Université de Strasbourg; FranciaFil: Howard, Eduardo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; ArgentinaFil: Pradeau-Aubreton, Karine. Université de Strasbourg; FranciaFil: Ruff, Marc. Université de Strasbourg; FranciaFil: Lamour, Valérie. Université de Strasbourg; FranciaNature Publishing Group2018-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/89288Bedez, Claire; Lotz, Christophe; Batisse, Claire; Broeck, Arnaud Vanden; Stote, Roland H.; et al.; Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain; Nature Publishing Group; Scientific Reports; 8; 1; 12-20182045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-018-27606-8info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-27606-8info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:27:07Zoai:ri.conicet.gov.ar:11336/89288instacron: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:34982025-10-15 14:27:08.259CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
title Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
spellingShingle Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
Bedez, Claire
DNA TOPOISOMERASE 2α
POST-TRANSLATIONAL MODIFICATIONS
title_short Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
title_full Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
title_fullStr Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
title_full_unstemmed Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
title_sort Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
dc.creator.none.fl_str_mv Bedez, Claire
Lotz, Christophe
Batisse, Claire
Broeck, Arnaud Vanden
Stote, Roland H.
Howard, Eduardo Ignacio
Pradeau-Aubreton, Karine
Ruff, Marc
Lamour, Valérie
author Bedez, Claire
author_facet Bedez, Claire
Lotz, Christophe
Batisse, Claire
Broeck, Arnaud Vanden
Stote, Roland H.
Howard, Eduardo Ignacio
Pradeau-Aubreton, Karine
Ruff, Marc
Lamour, Valérie
author_role author
author2 Lotz, Christophe
Batisse, Claire
Broeck, Arnaud Vanden
Stote, Roland H.
Howard, Eduardo Ignacio
Pradeau-Aubreton, Karine
Ruff, Marc
Lamour, Valérie
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DNA TOPOISOMERASE 2α
POST-TRANSLATIONAL MODIFICATIONS
topic DNA TOPOISOMERASE 2α
POST-TRANSLATIONAL MODIFICATIONS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Type 2 DNA topoisomerases (Top2) are critical components of key protein complexes involved in DNA replication, chromosome condensation and segregation, as well as gene transcription. The Top2 were found to be the main targets of anticancer agents, leading to intensive efforts to understand their functional and physiological role as well as their molecular structure. Post-translational modifications have been reported to influence Top2 enzyme activities in particular those of the mammalian Top2α isoform. In this study, we identified phosphorylation, and for the first time, acetylation sites in the human Top2α isoform produced in eukaryotic expression systems. Structural analysis revealed that acetylation sites are clustered on the catalytic domains of the homodimer while phosphorylation sites are located in the C-terminal domain responsible for nuclear localization. Biochemical analysis of the eukaryotic-specific K168 residue in the ATPase domain shows that acetylation affects a key position regulating ATP hydrolysis through the modulation of dimerization. Our findings suggest that acetylation of specific sites involved in the allosteric regulation of human Top2 may provide a mechanism for modulation of its catalytic activity.
Fil: Bedez, Claire. Université de Strasbourg; Francia
Fil: Lotz, Christophe. Université de Strasbourg; Francia
Fil: Batisse, Claire. Université de Strasbourg; Francia
Fil: Broeck, Arnaud Vanden. Université de Strasbourg; Francia
Fil: Stote, Roland H.. Université de Strasbourg; Francia
Fil: Howard, Eduardo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina
Fil: Pradeau-Aubreton, Karine. Université de Strasbourg; Francia
Fil: Ruff, Marc. Université de Strasbourg; Francia
Fil: Lamour, Valérie. Université de Strasbourg; Francia
description Type 2 DNA topoisomerases (Top2) are critical components of key protein complexes involved in DNA replication, chromosome condensation and segregation, as well as gene transcription. The Top2 were found to be the main targets of anticancer agents, leading to intensive efforts to understand their functional and physiological role as well as their molecular structure. Post-translational modifications have been reported to influence Top2 enzyme activities in particular those of the mammalian Top2α isoform. In this study, we identified phosphorylation, and for the first time, acetylation sites in the human Top2α isoform produced in eukaryotic expression systems. Structural analysis revealed that acetylation sites are clustered on the catalytic domains of the homodimer while phosphorylation sites are located in the C-terminal domain responsible for nuclear localization. Biochemical analysis of the eukaryotic-specific K168 residue in the ATPase domain shows that acetylation affects a key position regulating ATP hydrolysis through the modulation of dimerization. Our findings suggest that acetylation of specific sites involved in the allosteric regulation of human Top2 may provide a mechanism for modulation of its catalytic activity.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
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/11336/89288
Bedez, Claire; Lotz, Christophe; Batisse, Claire; Broeck, Arnaud Vanden; Stote, Roland H.; et al.; Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain; Nature Publishing Group; Scientific Reports; 8; 1; 12-2018
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/89288
identifier_str_mv Bedez, Claire; Lotz, Christophe; Batisse, Claire; Broeck, Arnaud Vanden; Stote, Roland H.; et al.; Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain; Nature Publishing Group; Scientific Reports; 8; 1; 12-2018
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-018-27606-8
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-27606-8
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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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_ 1846082724108959744
score 13.22299

Publicaciones similares