Machado-Silva, A., Teixeira, S. M.R., Franco, G. R., Macedo, A. M., Pena, S. D.J., McCulloch, R. and Machado, C. R. (2008) Mismatch repair in Trypanosoma brucei: Heterologous expression of MSH2 from Trypanosoma cruzi provides new insights into the response to oxidative damage. Gene, 411(1-2), pp. 19-26. (doi: 10.1016/j.gene.2007.12.021)
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Publisher's URL: http://dx.doi.org/10.1016/j.gene.2007.12.021
Abstract
Trypanosomes are unicellular eukaryotes that cause disease in humans and other mammals. <i>Trypanosoma cruzi</i> and <i>Trypanosoma brucei</i> are the causative agents, respectively, of Chagas disease in the Americas and sleeping sickness in sub-Saharan Africa. To better comprehend the interaction of these parasites with their hosts, understanding the mechanisms involved in the generation of genetic variability is critical. One such mechanism is mismatch repair (MMR), which has a crucial, evolutionarily conserved role in maintaining the fidelity of DNA replication, as well as acting in other cellular processes, such as DNA recombination. Here we have attempted to complement <i>T. Brucei</i> MMR through the expression of MSH2 from <i>T. cruzi.</i> Our results show that <i>T. Brucei</i> MSH2-null mutants are more sensitive to hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) than wild type cells, suggesting the involvement of MSH2 in the response to oxidative stress in this parasite. This phenotype is reverted by the expression of either the <i>T. Cruzi</i> or the <i>T. Brucei</i> MSH2 protein in the MSH2-null mutants. In contrast, MMR complementation, as assessed by resistance to N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) and microsatellite instability, was not achieved by the heterologous expression ofT. cruzi MSH2. This finding, associated to the demonstration that mutation of MLH1, another component of the MMR system, did not affect sensitivity of T. brucei cells to H<sub>2</sub>O<sub>2</sub>, suggests an additional role of MSH2 in dealing with oxidative damage in these parasites, which may occur independently of MMR.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | McCulloch, Professor Richard |
Authors: | Machado-Silva, A., Teixeira, S. M.R., Franco, G. R., Macedo, A. M., Pena, S. D.J., McCulloch, R., and Machado, C. R. |
Subjects: | Q Science > QR Microbiology > QR180 Immunology |
College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Gene |
Publisher: | Elsevier |
ISSN: | 0378-1119 |
ISSN (Online): | 1879-0038 |
Published Online: | 02 January 2008 |
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