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

Bruno Luiz Fonseca Schamber-Reis, Sheila Nardelli, Carlos Gustavo Régis-Silva, Priscila Carneiro Campos, Paula Gonalves Cerqueira, Sabrina Almeida Lima, Glória Regina Franco, Andrea Mara MacEdo, Sergio Danilo Junho Pena, Christophe Cazaux, Jean Sébastien Hoffmann, Maria Cristina Mac Hado Motta, Sergio Schenkman, Santuza Maria Ribeiro Teixeira, Carlos Renato MacHado

Research output: Articles / NotesScientific Articlepeer-review

23 Scopus citations


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-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.

Original languageEnglish
Pages (from-to)122-131
Number of pages10
JournalMolecular and Biochemical Parasitology
Issue number2
StatePublished - Jun 2012
Externally publishedYes


  • DNA repair
  • Kinetoplast
  • Oxidative stress
  • Oxoguanine
  • Trypanosoma cruzi


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