Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses

Autores
Reigada, Chantal; Martínez Sayé, Melisa Soledad; Di Girolamo, Fabio Augusto; Valera Vera, Edward Augusto; Pereira, Claudio Alejandro; Miranda, Mariana Reneé
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND NME23/NDPKs are well conserved proteins found in all living organisms. In addition to being nucleoside diphosphate kinases (NDPK), they are multifunctional enzymes involved in different processes such as DNA stability, gene regulation and DNA repair among others. TcNDPK1 is the canonical NDPK isoform present in Trypanosoma cruzi, which has nuclease activity and DNA-binding properties in vitro. OBJECTIVES In the present study we explored the role of TcNDPK1 in DNA damage responses. METHODS TcNDPK1 was expressed in mutant bacteria and yeasts and over-expressed in epimastigotes. Mutation frequencies, tolerance to genotoxic agents and activity of DNA repair enzymes were evaluated. FINDINGS Bacteria decreased about 15-folds the spontaneous mutation rate and yeasts were more resistant to hydrogen peroxide and to UV radiation than controls. Parasites overexpressing TcNDPK1 were able to withstand genotoxic stresses caused by hydrogen peroxide, phleomycin and hidroxyurea. They also presented less genomic damage and augmented levels of poly(ADP) ribose and poly(ADP)ribose polymerase, an enzyme involved in DNA repair. MAIN CONCLUSION These results strongly suggest a novel function for TcNDPK1; its involvement in the maintenance of parasite’s genome integrity.
Fil: Reigada, Chantal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Martínez Sayé, Melisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Di Girolamo, Fabio Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Valera Vera, Edward Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Miranda, Mariana Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Materia
DNA DAMAGE
DNA REPAIR
NDPK
NUCLEOSIDE DIPHOSPHATE KINASE
TRYPANOSOMA CRUZI
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/117153
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/117153
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responsesReigada, ChantalMartínez Sayé, Melisa SoledadDi Girolamo, Fabio AugustoValera Vera, Edward AugustoPereira, Claudio AlejandroMiranda, Mariana ReneéDNA DAMAGEDNA REPAIRNDPKNUCLEOSIDE DIPHOSPHATE KINASETRYPANOSOMA CRUZIhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1BACKGROUND NME23/NDPKs are well conserved proteins found in all living organisms. In addition to being nucleoside diphosphate kinases (NDPK), they are multifunctional enzymes involved in different processes such as DNA stability, gene regulation and DNA repair among others. TcNDPK1 is the canonical NDPK isoform present in Trypanosoma cruzi, which has nuclease activity and DNA-binding properties in vitro. OBJECTIVES In the present study we explored the role of TcNDPK1 in DNA damage responses. METHODS TcNDPK1 was expressed in mutant bacteria and yeasts and over-expressed in epimastigotes. Mutation frequencies, tolerance to genotoxic agents and activity of DNA repair enzymes were evaluated. FINDINGS Bacteria decreased about 15-folds the spontaneous mutation rate and yeasts were more resistant to hydrogen peroxide and to UV radiation than controls. Parasites overexpressing TcNDPK1 were able to withstand genotoxic stresses caused by hydrogen peroxide, phleomycin and hidroxyurea. They also presented less genomic damage and augmented levels of poly(ADP) ribose and poly(ADP)ribose polymerase, an enzyme involved in DNA repair. MAIN CONCLUSION These results strongly suggest a novel function for TcNDPK1; its involvement in the maintenance of parasite’s genome integrity.Fil: Reigada, Chantal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Martínez Sayé, Melisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Di Girolamo, Fabio Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Valera Vera, Edward Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Miranda, Mariana Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFundação Oswaldo Cruz2020-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/117153Reigada, Chantal; Martínez Sayé, Melisa Soledad; Di Girolamo, Fabio Augusto; Valera Vera, Edward Augusto; Pereira, Claudio Alejandro; et al.; Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses; Fundação Oswaldo Cruz; Memórias do Instituto Oswaldo Cruz; 115; 6; 7-2020; 1-90074-02761678-8060CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762020000100329&tlng=eninfo:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/830257v1.fullinfo:eu-repo/semantics/altIdentifier/doi/10.1590/0074-02760200019info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:51:25Zoai:ri.conicet.gov.ar:11336/117153instacron: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 09:51:25.472CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses
title Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses
spellingShingle Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses
Reigada, Chantal
DNA DAMAGE
DNA REPAIR
NDPK
NUCLEOSIDE DIPHOSPHATE KINASE
TRYPANOSOMA CRUZI
title_short Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses
title_full Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses
title_fullStr Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses
title_full_unstemmed Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses
title_sort Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses
dc.creator.none.fl_str_mv Reigada, Chantal
Martínez Sayé, Melisa Soledad
Di Girolamo, Fabio Augusto
Valera Vera, Edward Augusto
Pereira, Claudio Alejandro
Miranda, Mariana Reneé
author Reigada, Chantal
author_facet Reigada, Chantal
Martínez Sayé, Melisa Soledad
Di Girolamo, Fabio Augusto
Valera Vera, Edward Augusto
Pereira, Claudio Alejandro
Miranda, Mariana Reneé
author_role author
author2 Martínez Sayé, Melisa Soledad
Di Girolamo, Fabio Augusto
Valera Vera, Edward Augusto
Pereira, Claudio Alejandro
Miranda, Mariana Reneé
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv DNA DAMAGE
DNA REPAIR
NDPK
NUCLEOSIDE DIPHOSPHATE KINASE
TRYPANOSOMA CRUZI
topic DNA DAMAGE
DNA REPAIR
NDPK
NUCLEOSIDE DIPHOSPHATE KINASE
TRYPANOSOMA CRUZI
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv BACKGROUND NME23/NDPKs are well conserved proteins found in all living organisms. In addition to being nucleoside diphosphate kinases (NDPK), they are multifunctional enzymes involved in different processes such as DNA stability, gene regulation and DNA repair among others. TcNDPK1 is the canonical NDPK isoform present in Trypanosoma cruzi, which has nuclease activity and DNA-binding properties in vitro. OBJECTIVES In the present study we explored the role of TcNDPK1 in DNA damage responses. METHODS TcNDPK1 was expressed in mutant bacteria and yeasts and over-expressed in epimastigotes. Mutation frequencies, tolerance to genotoxic agents and activity of DNA repair enzymes were evaluated. FINDINGS Bacteria decreased about 15-folds the spontaneous mutation rate and yeasts were more resistant to hydrogen peroxide and to UV radiation than controls. Parasites overexpressing TcNDPK1 were able to withstand genotoxic stresses caused by hydrogen peroxide, phleomycin and hidroxyurea. They also presented less genomic damage and augmented levels of poly(ADP) ribose and poly(ADP)ribose polymerase, an enzyme involved in DNA repair. MAIN CONCLUSION These results strongly suggest a novel function for TcNDPK1; its involvement in the maintenance of parasite’s genome integrity.
Fil: Reigada, Chantal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Martínez Sayé, Melisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Di Girolamo, Fabio Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Valera Vera, Edward Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Miranda, Mariana Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
description BACKGROUND NME23/NDPKs are well conserved proteins found in all living organisms. In addition to being nucleoside diphosphate kinases (NDPK), they are multifunctional enzymes involved in different processes such as DNA stability, gene regulation and DNA repair among others. TcNDPK1 is the canonical NDPK isoform present in Trypanosoma cruzi, which has nuclease activity and DNA-binding properties in vitro. OBJECTIVES In the present study we explored the role of TcNDPK1 in DNA damage responses. METHODS TcNDPK1 was expressed in mutant bacteria and yeasts and over-expressed in epimastigotes. Mutation frequencies, tolerance to genotoxic agents and activity of DNA repair enzymes were evaluated. FINDINGS Bacteria decreased about 15-folds the spontaneous mutation rate and yeasts were more resistant to hydrogen peroxide and to UV radiation than controls. Parasites overexpressing TcNDPK1 were able to withstand genotoxic stresses caused by hydrogen peroxide, phleomycin and hidroxyurea. They also presented less genomic damage and augmented levels of poly(ADP) ribose and poly(ADP)ribose polymerase, an enzyme involved in DNA repair. MAIN CONCLUSION These results strongly suggest a novel function for TcNDPK1; its involvement in the maintenance of parasite’s genome integrity.
publishDate 2020
dc.date.none.fl_str_mv 2020-07
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/11336/117153
Reigada, Chantal; Martínez Sayé, Melisa Soledad; Di Girolamo, Fabio Augusto; Valera Vera, Edward Augusto; Pereira, Claudio Alejandro; et al.; Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses; Fundação Oswaldo Cruz; Memórias do Instituto Oswaldo Cruz; 115; 6; 7-2020; 1-9
0074-0276
1678-8060
CONICET Digital
CONICET
url http://hdl.handle.net/11336/117153
identifier_str_mv Reigada, Chantal; Martínez Sayé, Melisa Soledad; Di Girolamo, Fabio Augusto; Valera Vera, Edward Augusto; Pereira, Claudio Alejandro; et al.; Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses; Fundação Oswaldo Cruz; Memórias do Instituto Oswaldo Cruz; 115; 6; 7-2020; 1-9
0074-0276
1678-8060
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.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762020000100329&tlng=en
info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/830257v1.full
info:eu-repo/semantics/altIdentifier/doi/10.1590/0074-02760200019
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Fundação Oswaldo Cruz
publisher.none.fl_str_mv Fundação Oswaldo Cruz
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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