1. Trypanosoma cruzi MSH2: Functional analyses on different parasite strains provide evidences for a role on the oxidative stress response.
- Author
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Campos PC, Silva VG, Furtado C, Machado-Silva A, Darocha WD, Peloso EF, Gadelha FR, Medeiros MH, Lana Gde C, Chen Y, Barnes RL, Passos-Silva DG, McCulloch R, Machado CR, and Teixeira SM
- Subjects
- Adenosine Triphosphatases metabolism, Cisplatin pharmacology, Cross-Linking Reagents pharmacology, DNA Damage drug effects, DNA Mismatch Repair, DNA, Mitochondrial genetics, Gene Expression Regulation, Gene Knockout Techniques, Hydrogen Peroxide pharmacology, Molecular Sequence Data, MutS Homolog 2 Protein genetics, Mutation, Oxidants pharmacology, Protozoan Proteins genetics, Trypanosoma brucei brucei enzymology, Trypanosoma brucei brucei genetics, Trypanosoma cruzi drug effects, MutS Homolog 2 Protein metabolism, Oxidative Stress, Protozoan Proteins metabolism, Trypanosoma cruzi enzymology, Trypanosoma cruzi genetics
- 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., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2011
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