Trypanosoma cruzi MSH2: Functional analyses on different parasite strains provide evidences for a role on the oxidative stress response

Priscila C. Campos, Viviane G. Silva, Carolina Furtado, Alice MacHado-Silva, Wanderson D. Darocha, Eduardo F. Peloso, Fernanda R. Gadelha, Marisa H.G. Medeiros, Gustavo De Carvalho Lana, Ying Chen, Rebecca L. Barnes, Danielle Gomes Passos-Silva, Richard McCulloch, Carlos Renato MacHado, Santuza M.R. Teixeira

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Components of the DNA mismatch repair (MMR) pathway are major players in processes known to generate genetic diversity, such as mutagenesis and DNA recombination. Trypanosoma cruzi, the protozoan parasite that causes Chagas disease has a highly heterogeneous population, composed of a pool of strains with distinct characteristics. Studies with a number of molecular markers identified up to six groups in the T. cruzi population, which showed distinct levels of genetic variability. To investigate the molecular basis for such differences, we analyzed the T. cruzi MSH2 gene, which encodes a key component of MMR, and showed the existence of distinct isoforms of this protein. Here we compared cell survival rates after exposure to genotoxic agents and levels of oxidative stress-induced DNA in different parasite strains. Analyses of msh2 mutants in both T. cruzi and T. brucei were also used to investigate the role of Tcmsh2 in the response to various DNA damaging agents. The results suggest that the distinct MSH2 isoforms have differences in their activity. More importantly, they also indicate that, in addition to its role in MMR, TcMSH2 acts in the parasite response to oxidative stress through a novel mitochondrial function that may be conserved in T. brucei.

Original languageEnglish
Pages (from-to)8-16
Number of pages9
JournalMolecular and Biochemical Parasitology
Volume176
Issue number1
DOIs
StatePublished - Mar 2011
Externally publishedYes

Keywords

  • DNA repair
  • MSH2
  • Oxidative stress
  • Trypanosoma brucei
  • Trypanosoma cruzi

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