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The oxidative lesion 8-oxoguanine (8-oxoG) is removed during base excision repair by the 8-oxoguanine DNA glycosylase 1 (Ogg1). This lesion can erroneously pair with adenine, and the excision of this damaged base by Ogg1 enables the insertion of a guanine and prevents DNA mutation. In this report, we identified and characterized Ogg1 from the protozoan parasite  Trypanosoma cruzi  (TcOgg1), the causative agent of Chagas disease. Like most living organisms,  T. cruzi  is susceptible to oxidative stress, hence DNA repair is essential for its survival and improvement of infection. We verified that the  TcOGG1  gene encodes an 8-oxoG DNA glycosylase by complementing an Ogg1-defective  Saccharomyces cerevisiae  strain. Heterologous expression of  TcOGG1  reestablished the mutation frequency of the yeast mutant  ogg1 − / −   (CD138) to wild type levels. We also demonstrate that the overexpression of  TcOGG1  increases  T. cruzi  sensitivity to hydrogen peroxide (H 2 O 2 ). Analysis of DNA lesions using quantitative PCR suggests that the increased susceptibility to H 2 O 2  of  TcOGG1 -overexpressor could be a consequence of uncoupled BER in abasic sites and/or strand breaks generated after TcOgg1 removes 8-oxoG, which are not rapidly repaired by the subsequent BER enzymes. This hypothesis is supported by the observation that  TcOGG1 -overexpressors have reduced levels of 8-oxoG both in the nucleus and in the parasite mitochondrion. The localization of TcOgg1 was examined in parasite transfected with a TcOgg1-GFP fusion, which confirmed that this enzyme is in both organelles. Taken together, our data indicate that  T. cruzi  has a functional Ogg1 ortholog that participates in nuclear and mitochondrial BER.

Functional Characterization of 8-Oxoguanine DNA Glycosylase of Trypanosoma cruzi