The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions.

Gomes Passos Silva, D. et al. (2018) The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions. PLoS Neglected Tropical Diseases, 12(11), e0006875. (doi:10.1371/journal.pntd.0006875) (PMID:30422982) (PMCID:PMC6258567)

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Abstract

In Trypanosoma cruzi, the etiologic agent of Chagas disease, Rad51 (TcRad51) is a central enzyme for homologous recombination. Here we describe the different roles of TcRad51 in DNA repair. Epimastigotes of T. cruzi overexpressing TcRAD51 presented abundant TcRad51-labeled foci before gamma irradiation treatment, and a faster growth recovery when compared to single-knockout epimastigotes for RAD51. Overexpression of RAD51 also promoted increased resistance against hydrogen peroxide treatment, while the single-knockout epimastigotes for RAD51 exhibited increased sensitivity to this oxidant agent, which indicates a role for this gene in the repair of DNA oxidative lesions. In contrast, TcRad51 was not involved in the repair of crosslink lesions promoted by UV light and cisplatin treatment. Also, RAD51 single-knockout epimastigotes showed a similar growth rate to that exhibited by wild-type ones after treatment with hydroxyurea, but an increased sensitivity to methyl methane sulfonate. Besides its role in epimastigotes, TcRad51 is also important during mammalian infection, as shown by increased detection of T. cruzi cells overexpressing RAD51, and decreased detection of single-knockout cells for RAD51, in both fibroblasts and macrophages infected with amastigotes. Besides that, RAD51-overexpressing parasites infecting mice also presented increased infectivity and higher resistance against benznidazole. We thus show that TcRad51 is involved in the repair of DNA double strands breaks and oxidative lesions in two different T. cruzi developmental stages, possibly playing an important role in the infectivity of this parasite.

Item Type:Articles
Additional Information:Funding: Fundação de Amparo a Pesquisa de Minas Gerais (grant numbers: APQ-02308-13, APQ-00827-15), Conselho Nacional de Desenvolvimento Científico e Tecnológico (grant number: 444334/2014-9), Fundação de Amparo a Pesquisa de São Paulo (grant numbers: 17/07092-9), Pró-Reitoria de Pesquisa/UFMG.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McCulloch, Professor Richard
Creator Roles:
McCulloch, R.Conceptualization, Formal analysis, Writing – original draft, Writing – review and editing
Authors: Gomes Passos Silva, D., da Silva Santos, S., Nardelli, S. C., Mendes, I. C., Freire, A. C. G., Repolês, B. M., Resende, B. C., Costa-Silva, H. M., da Silva, V. S., Oliveira, K. A. d., Oliveira, C. F. B., Vilela, L. F. F., Nagem, R. A. P., Franco, G. R., Macedo, A. M., Pena, S. D. J., Tahara, E. B., Sales Junior, P. A., Moreira, D. S., Teixeira, S. M. R., McCulloch, R., Virgilio, S., Tosi, L. R. O., Schenkman, S., Andrade, L. O., Murta, S. M. F., and Machado, C. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2018 Gomes Passos Silva et al.
First Published:First published in PLoS Neglected Tropical Diseases 12(11): e0006875
Publisher Policy:Reproduced under a Creative Commons License

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