دورية أكاديمية
The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions.
العنوان: | The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions. |
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المؤلفون: | Gomes Passos Silva D; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., da Silva Santos S; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.; Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte, MG, Brazil., Nardelli SC; Instituto Carlos Chagas/FIOCRUZ, Rua Professor Algacyr Munhoz Mader 3775, Curitiba, PR, Brazil., Mendes IC; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Freire ACG; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Repolês BM; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Resende BC; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Costa-Silva HM; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., da Silva VS; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Oliveira KA; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Oliveira CFB; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Vilela LFF; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Nagem RAP; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Franco GR; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Macedo AM; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Pena SDJ; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Tahara EB; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Sales Junior PA; Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte, MG, Brazil., Moreira DS; Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte, MG, Brazil., Teixeira SMR; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., McCulloch R; Wellcome Trust Centre for Molecular Parasitology, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom., Virgilio S; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Tosi LRO; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Schenkman S; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, São Paulo, Brazil., Andrade LO; Departamento de Morfologia, ICB, Universidade Federal de Minas Gerais, Caixa Postal 486, Belo Horizonte, MG, Brazil., Murta SMF; Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte, MG, Brazil., Machado CR; Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. |
المصدر: | PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2018 Nov 13; Vol. 12 (11), pp. e0006875. Date of Electronic Publication: 2018 Nov 13 (Print Publication: 2018). |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: eCollection Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science |
مواضيع طبية MeSH: | DNA Breaks, Double-Stranded*/radiation effects , DNA Repair*/radiation effects, Protozoan Proteins/*metabolism , Rad51 Recombinase/*metabolism , Trypanosoma cruzi/*enzymology , Trypanosoma cruzi/*genetics, Animals ; Chagas Disease/parasitology ; Humans ; Male ; Mice ; Oxidative Stress ; Protozoan Proteins/genetics ; Rad51 Recombinase/genetics ; Trypanosoma cruzi/metabolism ; Trypanosoma cruzi/radiation effects ; Ultraviolet Rays |
مستخلص: | 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. Competing Interests: The authors have declared that no competing interests exist. |
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المشرفين على المادة: | 0 (Protozoan Proteins) EC 2.7.7.- (Rad51 Recombinase) |
تواريخ الأحداث: | Date Created: 20181114 Date Completed: 20190121 Latest Revision: 20190121 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC6258567 |
DOI: | 10.1371/journal.pntd.0006875 |
PMID: | 30422982 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1935-2735 |
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DOI: | 10.1371/journal.pntd.0006875 |