DNA polymerase beta from Trypanosoma cruzi is involved in kinetoplast DNA replication and repair of oxidative lesions

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dc.contributor.authorSchamber-Reis, Bruno Luiz Fonseca
dc.contributor.authorNardelli, Sheila Cristina [UNIFESP]
dc.contributor.authorRegis-Silva, Carlos Gustavo
dc.contributor.authorCampos, Priscila Carneiro
dc.contributor.authorCerqueira, Paula Gonçalves
dc.contributor.authorLima, Sabrina Almeida
dc.contributor.authorFranco, Gloria Regina
dc.contributor.authorMacedo, Andréa Mara
dc.contributor.authorPena, Sergio Danilo Junho
dc.contributor.authorCazaux, Christophe
dc.contributor.authorHoffmann, Jean-Sebastien
dc.contributor.authorMotta, Maria Cristina Machado
dc.contributor.authorSchenkman, Sergio [UNIFESP]
dc.contributor.authorTeixeira, Santuza Maria Ribeiro
dc.contributor.authorMachado, Carlos Renato
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.contributor.institutionSuper Learning & Dev Ctr CESED
dc.contributor.institutionCNRS
dc.contributor.institutionUniv Toulouse
dc.date.accessioned2016-01-24T14:27:16Z
dc.date.available2016-01-24T14:27:16Z
dc.date.issued2012-06-01
dc.description.abstractSpecific DNA repair pathways from Trypanosoma cruzi are believed to protect genomic DNA and kinetoplast DNA (kDNA) from mutations. Particular pathways are supposed to operate in order to repair nucleotides oxidized by reactive oxygen species (ROS) during parasite infection, being 7,8-dihydro-8oxoguanine (8oxoG) a frequent and highly mutagenic base alteration. If unrepaired, 8oxoG can lead to cytotoxic base transversions during DNA replication. in mammals, DNA polymerase beta (Pol beta) is mainly involved in base excision repair (BER) of oxidative damage. However its biological role in T. cruzi is still unknown. We show, by immunofluorescence localization, that T. cruzi DNA polymerase beta (Tcpol beta) is restricted to the antipodal sites of kDNA in replicative epimastigote and amastigote developmental stages, being strictly localized to kDNA antipodal sites between G1/S and early G2 phase in replicative epimastigotes. Nevertheless, this polymerase was detected inside the mitochondrial matrix of trypomastigote forms, which are not able to replicate in culture. Parasites over expressing Tcpol beta showed reduced levels of 8oxoG in kDNA and an increased survival after treatment with hydrogen peroxide when compared to control cells. However, this resistance was lost after treating Tcpol beta overexpressors with methoxiamine, a potent BER inhibitor. Curiously, a presumed DNA repair focus containing Tcpol beta was identified in the vicinity of kDNA of cultured wild type epimastigotes after treatment with hydrogen peroxide. Taken together our data suggest participation of Tcpol beta during kDNA replication and repair of oxidative DNA damage induced by genotoxic stress in this organelle. (C) 2012 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Fed Minas Gerais, Dept Biochem & Immunol, ICB UFMG, Inst Biol Sci, BR-31270901 Belo Horizonte, MG, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Hertha Meyer Cellular Ultra Struct Lab, Inst Biophys Carlos Chagas Filho, BR-21941 Rio de Janeiro, Brazil
dc.description.affiliationSuper Learning & Dev Ctr CESED, Sch Med Sci, Campina Grande, Paraiba, Brazil
dc.description.affiliationCNRS, Inst Pharmacol & Struct Biol, UMR5089, Toulouse, France
dc.description.affiliationUniv Toulouse, Toulouse, France
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipPRONEX
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorshipHoward Hughes Medical Institute
dc.description.sponsorshipIDCNPq: MCT/CNPq/MS-SCTIE-DECIT 25/2006-Estudo de Doencas Negligenciadas
dc.format.extent122-131
dc.identifierhttp://dx.doi.org/10.1016/j.molbiopara.2012.02.007
dc.identifier.citationMolecular and Biochemical Parasitology. Amsterdam: Elsevier B.V., v. 183, n. 2, p. 122-131, 2012.
dc.identifier.doi10.1016/j.molbiopara.2012.02.007
dc.identifier.fileWOS000303845400003.pdf
dc.identifier.issn0166-6851
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34910
dc.identifier.wosWOS:000303845400003
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofMolecular and Biochemical Parasitology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectDNA repairen
dc.subjectTrypanosoma cruzien
dc.subjectOxidative stressen
dc.subjectOxoguanineen
dc.subjectKinetoplasten
dc.titleDNA polymerase beta from Trypanosoma cruzi is involved in kinetoplast DNA replication and repair of oxidative lesionsen
dc.typeinfo:eu-repo/semantics/article
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