title: Trypanosoma cruzi MSH2: Functional analyses on different parasite strains provide evidences for a role on the oxidative stress response.
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.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Priscila C
authors.initials: PC
authors.lastname: Campos
authors.forename: Viviane G
authors.initials: VG
authors.lastname: Silva
authors.forename: Carolina
authors.initials: C
authors.lastname: Furtado
authors.forename: Alice
authors.initials: A
authors.lastname: Machado-Silva
authors.forename: Wanderson D
authors.initials: WD
authors.lastname: Darocha
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Peloso
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Gadelha
authors.forename: Marisa H G
authors.initials: MH
authors.lastname: Medeiros
authors.forename: Gustavo de Carvalho
authors.initials: Gde C
authors.lastname: Lana
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Barnes
authors.forename: Danielle Gomes
authors.initials: DG
authors.lastname: Passos-Silva
authors.forename: Richard
authors.initials: R
authors.lastname: McCulloch
authors.forename: Carlos Renato
authors.initials: CR
authors.lastname: Machado
authors.forename: Santuza M R
authors.initials: SM
authors.lastname: Teixeira
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D053843:DNA Mismatch Repair; D004272:DNA, Mitochondrial / Q000235:genetics; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000201:enzymology / Q000235:genetics; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*
chemical_list: D003432:Cross-Linking Reagents; D004272:DNA, Mitochondrial; D016877:Oxidants; D015800:Protozoan Proteins; D006861:Hydrogen Peroxide; D000251:Adenosine Triphosphatases; C435509:MSH2 protein, Trypanosoma cruzi; D051718:MutS Homolog 2 Protein; D002945:Cisplatin