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

dc.creatorReis, Bruno Luiz Fonseca Schamber
dc.creatorNardelli, Sheila
dc.creatorSilva, Carlos Gustavo Régis
dc.creatorCampos, Priscila Carneiro
dc.creatorCerqueira, Paula Gonçalves
dc.creatorLima, Sabrina Almeida
dc.creatorFranco, Glória Regina
dc.creatorMacedo, Andrea Mara
dc.creatorPena, Sergio Danilo Junho
dc.creatorCazaux, Christophe
dc.creatorHoffmann, Jean-Sébastien
dc.creatorMotta, Maria Cristina Machado
dc.creatorSchenkman, Sergio
dc.creatorTeixeira, Santuza Maria Ribeiro
dc.creatorMachado, Carlos Renato
dc.date2018-06-29T16:24:58Z
dc.date2018-06-29T16:24:58Z
dc.date2012
dc.date.accessioned2023-09-26T23:34:36Z
dc.date.available2023-09-26T23:34:36Z
dc.identifierREIS, B. L. F. S. et al. DNA polymerase beta from Trypanosoma cruzi is involved in kinetoplast DNA replication and repair of oxidative lesions. Molecular and Biochemical Parasitology, v. 183, p. 122– 131, 2012.
dc.identifier0166-6851
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/27201
dc.identifier10.1016/j.molbiopara.2012.02.007
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8892057
dc.descriptionSilva, Carlos Gustavo Régis. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.
dc.descriptionCNPq-Brazil (MCT/CNPq/MSSCTIE-DECIT 25/2006-Estudo de Doenc¸ as Negligenciadas), PRONEX and FAPEMIG.
dc.descriptionSpecific 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-8-oxoguanine (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 (Polβ) 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 (Tcpolβ) 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 Tcpolβ 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 Tcpolβ overexpressors with methoxiamine, a potent BER inhibitor. Curiously, a presumed DNA repair focus containing Tcpolβ was identified in the vicinity of kDNA of cultured wild type epimastigotes after treatment with hydrogen peroxide. Taken together our data suggest participation of Tcpolβ during kDNA replication and repair of oxidative DNA damage induced by genotoxic stress in this organelle.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsopen access
dc.subjectReparo de DNA
dc.subjectTrypanosoma cruzi
dc.subjectEstresse oxidativo
dc.subjectOxoguanine
dc.subjectKinetoplast
dc.subjectDNA repair
dc.subjectTrypanosoma cruzi
dc.subjectOxidative stress
dc.subjectOxoguanine
dc.subjectKinetoplast
dc.titleDNA polymerase beta from Trypanosoma cruzi is involved in kinetoplast DNA replication and repair of oxidative lesions
dc.typeArticle


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