The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions.
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 irradiat...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-11-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC6258567?pdf=render |
| _version_ | 1818251617249525760 |
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| author | Danielle Gomes Passos Silva Selma da Silva Santos Sheila C Nardelli Isabela Cecília Mendes Anna Cláudia Guimarães Freire Bruno Marçal Repolês Bruno Carvalho Resende Héllida Marina Costa-Silva Verônica Santana da Silva Karla Andrade de Oliveira Camila Franco Batista Oliveira Liza Figueiredo Felicori Vilela Ronaldo Alves Pinto Nagem Glória Regina Franco Andrea Mara Macedo Sergio Danilo Junho Pena Erich Birelli Tahara Policarpo Ademar Sales Junior Douglas Souza Moreira Santuza Maria Ribeiro Teixeira Richard McCulloch Stela Virgilio Luiz Ricardo Orsini Tosi Sergio Schenkman Luciana Oliveira Andrade Silvane Maria Fonseca Murta Carlos Renato Machado |
| author_facet | Danielle Gomes Passos Silva Selma da Silva Santos Sheila C Nardelli Isabela Cecília Mendes Anna Cláudia Guimarães Freire Bruno Marçal Repolês Bruno Carvalho Resende Héllida Marina Costa-Silva Verônica Santana da Silva Karla Andrade de Oliveira Camila Franco Batista Oliveira Liza Figueiredo Felicori Vilela Ronaldo Alves Pinto Nagem Glória Regina Franco Andrea Mara Macedo Sergio Danilo Junho Pena Erich Birelli Tahara Policarpo Ademar Sales Junior Douglas Souza Moreira Santuza Maria Ribeiro Teixeira Richard McCulloch Stela Virgilio Luiz Ricardo Orsini Tosi Sergio Schenkman Luciana Oliveira Andrade Silvane Maria Fonseca Murta Carlos Renato Machado |
| author_sort | Danielle Gomes Passos Silva |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T16:11:08Z |
| format | Article |
| id | doaj.art-36c29e39f2654429899460add329f872 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-12T16:11:08Z |
| publishDate | 2018-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-36c29e39f2654429899460add329f8722022-12-22T00:19:11ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352018-11-011211e000687510.1371/journal.pntd.0006875The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions.Danielle Gomes Passos SilvaSelma da Silva SantosSheila C NardelliIsabela Cecília MendesAnna Cláudia Guimarães FreireBruno Marçal RepolêsBruno Carvalho ResendeHéllida Marina Costa-SilvaVerônica Santana da SilvaKarla Andrade de OliveiraCamila Franco Batista OliveiraLiza Figueiredo Felicori VilelaRonaldo Alves Pinto NagemGlória Regina FrancoAndrea Mara MacedoSergio Danilo Junho PenaErich Birelli TaharaPolicarpo Ademar Sales JuniorDouglas Souza MoreiraSantuza Maria Ribeiro TeixeiraRichard McCullochStela VirgilioLuiz Ricardo Orsini TosiSergio SchenkmanLuciana Oliveira AndradeSilvane Maria Fonseca MurtaCarlos Renato MachadoIn 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.http://europepmc.org/articles/PMC6258567?pdf=render |
| spellingShingle | Danielle Gomes Passos Silva Selma da Silva Santos Sheila C Nardelli Isabela Cecília Mendes Anna Cláudia Guimarães Freire Bruno Marçal Repolês Bruno Carvalho Resende Héllida Marina Costa-Silva Verônica Santana da Silva Karla Andrade de Oliveira Camila Franco Batista Oliveira Liza Figueiredo Felicori Vilela Ronaldo Alves Pinto Nagem Glória Regina Franco Andrea Mara Macedo Sergio Danilo Junho Pena Erich Birelli Tahara Policarpo Ademar Sales Junior Douglas Souza Moreira Santuza Maria Ribeiro Teixeira Richard McCulloch Stela Virgilio Luiz Ricardo Orsini Tosi Sergio Schenkman Luciana Oliveira Andrade Silvane Maria Fonseca Murta Carlos Renato Machado 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 |
| title | The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions. |
| title_full | The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions. |
| title_fullStr | The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions. |
| title_full_unstemmed | The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions. |
| title_short | The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions. |
| title_sort | in vivo and in vitro roles of trypanosoma cruzi rad51 in the repair of dna double strand breaks and oxidative lesions |
| url | http://europepmc.org/articles/PMC6258567?pdf=render |
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