Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei

Autores
Haikarainen, Teemu; Schlesinger, Mariana; Obaji, Ezeogo; Fernandez Villamil, Silvia Hebe; Lehtio, Lari
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness.It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs.PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure andsubcellular localization of T. brucei PARP. T. brucei PARP was found to be selectively activated by 5′phosphorylated and 3′ phosphorylated DNA breaks. Importantly, the N-terminal region is responsible for high-affinity DNA-binding and required for DNA-dependent enzymatic activation. This module is also required for nuclear localization of the protein in response to oxidative stress. Solution structures of activating and non-activating PARP-DNA complexes were determined with small-angle X-ray scattering revealing distinct differences in their DNA-binding modes.
Fil: Haikarainen, Teemu. University of Oulu; Finlandia
Fil: Schlesinger, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Obaji, Ezeogo. University of Oulu; Finlandia
Fil: Fernandez Villamil, Silvia Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Lehtio, Lari. University of Oulu; Finlandia
Materia
TRYPANOSOMA BRUCEI
PARP
DNA-DEPENDENT ACTIVATION
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:11336/40878
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma bruceiHaikarainen, TeemuSchlesinger, MarianaObaji, EzeogoFernandez Villamil, Silvia HebeLehtio, LariTRYPANOSOMA BRUCEIPARPDNA-DEPENDENT ACTIVATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness.It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs.PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure andsubcellular localization of T. brucei PARP. T. brucei PARP was found to be selectively activated by 5′phosphorylated and 3′ phosphorylated DNA breaks. Importantly, the N-terminal region is responsible for high-affinity DNA-binding and required for DNA-dependent enzymatic activation. This module is also required for nuclear localization of the protein in response to oxidative stress. Solution structures of activating and non-activating PARP-DNA complexes were determined with small-angle X-ray scattering revealing distinct differences in their DNA-binding modes.Fil: Haikarainen, Teemu. University of Oulu; FinlandiaFil: Schlesinger, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Obaji, Ezeogo. University of Oulu; FinlandiaFil: Fernandez Villamil, Silvia Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lehtio, Lari. University of Oulu; FinlandiaNature Publishing Group2017-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/40878Haikarainen, Teemu; Schlesinger, Mariana; Obaji, Ezeogo; Fernandez Villamil, Silvia Hebe; Lehtio, Lari; Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei; Nature Publishing Group; Scientific Reports; 7; 1; 6-2017; 1-122045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-03751-4info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-017-03751-4info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:37Zoai:ri.conicet.gov.ar:11336/40878instacron: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:34982025-09-29 09:34:37.518CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
title Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
spellingShingle Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
Haikarainen, Teemu
TRYPANOSOMA BRUCEI
PARP
DNA-DEPENDENT ACTIVATION
title_short Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
title_full Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
title_fullStr Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
title_full_unstemmed Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
title_sort Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei
dc.creator.none.fl_str_mv Haikarainen, Teemu
Schlesinger, Mariana
Obaji, Ezeogo
Fernandez Villamil, Silvia Hebe
Lehtio, Lari
author Haikarainen, Teemu
author_facet Haikarainen, Teemu
Schlesinger, Mariana
Obaji, Ezeogo
Fernandez Villamil, Silvia Hebe
Lehtio, Lari
author_role author
author2 Schlesinger, Mariana
Obaji, Ezeogo
Fernandez Villamil, Silvia Hebe
Lehtio, Lari
author2_role author
author
author
author
dc.subject.none.fl_str_mv TRYPANOSOMA BRUCEI
PARP
DNA-DEPENDENT ACTIVATION
topic TRYPANOSOMA BRUCEI
PARP
DNA-DEPENDENT ACTIVATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness.It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs.PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure andsubcellular localization of T. brucei PARP. T. brucei PARP was found to be selectively activated by 5′phosphorylated and 3′ phosphorylated DNA breaks. Importantly, the N-terminal region is responsible for high-affinity DNA-binding and required for DNA-dependent enzymatic activation. This module is also required for nuclear localization of the protein in response to oxidative stress. Solution structures of activating and non-activating PARP-DNA complexes were determined with small-angle X-ray scattering revealing distinct differences in their DNA-binding modes.
Fil: Haikarainen, Teemu. University of Oulu; Finlandia
Fil: Schlesinger, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Obaji, Ezeogo. University of Oulu; Finlandia
Fil: Fernandez Villamil, Silvia Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Lehtio, Lari. University of Oulu; Finlandia
description Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness.It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs.PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure andsubcellular localization of T. brucei PARP. T. brucei PARP was found to be selectively activated by 5′phosphorylated and 3′ phosphorylated DNA breaks. Importantly, the N-terminal region is responsible for high-affinity DNA-binding and required for DNA-dependent enzymatic activation. This module is also required for nuclear localization of the protein in response to oxidative stress. Solution structures of activating and non-activating PARP-DNA complexes were determined with small-angle X-ray scattering revealing distinct differences in their DNA-binding modes.
publishDate 2017
dc.date.none.fl_str_mv 2017-06
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/11336/40878
Haikarainen, Teemu; Schlesinger, Mariana; Obaji, Ezeogo; Fernandez Villamil, Silvia Hebe; Lehtio, Lari; Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei; Nature Publishing Group; Scientific Reports; 7; 1; 6-2017; 1-12
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/40878
identifier_str_mv Haikarainen, Teemu; Schlesinger, Mariana; Obaji, Ezeogo; Fernandez Villamil, Silvia Hebe; Lehtio, Lari; Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei; Nature Publishing Group; Scientific Reports; 7; 1; 6-2017; 1-12
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/doi/10.1038/s41598-017-03751-4
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-017-03751-4
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
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score 13.070432

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