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

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

Author Schamber-Reis, Bruno Luiz Fonseca Google Scholar
Nardelli, Sheila Cristina Autor UNIFESP Google Scholar
Regis-Silva, Carlos Gustavo Google Scholar
Campos, Priscila Carneiro Google Scholar
Cerqueira, Paula Gonçalves Google Scholar
Lima, Sabrina Almeida Google Scholar
Franco, Gloria Regina Google Scholar
Macedo, Andréa Mara Google Scholar
Pena, Sergio Danilo Junho Google Scholar
Cazaux, Christophe Google Scholar
Hoffmann, Jean-Sebastien Google Scholar
Motta, Maria Cristina Machado Google Scholar
Schenkman, Sergio Autor UNIFESP Google Scholar
Teixeira, Santuza Maria Ribeiro Google Scholar
Machado, Carlos Renato Google Scholar
Institution Universidade Federal de Minas Gerais (UFMG)
Universidade Federal de São Paulo (UNIFESP)
Universidade Federal do Rio de Janeiro (UFRJ)
Super Learning & Dev Ctr CESED
Univ Toulouse
Abstract Specific 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.
Keywords DNA repair
Trypanosoma cruzi
Oxidative stress
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
Howard Hughes Medical Institute
Grant number CNPq: MCT/CNPq/MS-SCTIE-DECIT 25/2006-Estudo de Doencas Negligenciadas
Date 2012-06-01
Published in Molecular and Biochemical Parasitology. Amsterdam: Elsevier B.V., v. 183, n. 2, p. 122-131, 2012.
ISSN 0166-6851 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 122-131
Origin http://dx.doi.org/10.1016/j.molbiopara.2012.02.007
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000303845400003
URI http://repositorio.unifesp.br/handle/11600/34910

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