DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi

Detalhes bibliográficos
Autor(a) principal: Costa-Silva, Héllida Marina
Data de Publicação: 2021
Outros Autores: Resende, Bruno Carvalho, Umaki, Adriana Castilhos Souza, Prado, Willian, Silva, Marcelo Santos da, Virgílio, Stela, Macedo, Andrea Mara, Pena, Sérgio Danilo Junho, Tahara, Erich Birelli, Tosi, Luiz Ricardo Orsini, Elias, Maria Carolina, Andrade, Luciana Oliveira, Reis-Cunha, João Luís, Franco, Glória Regina, Fragoso, Stenio Perdigão, Machado, Carlos Renato
Tipo de documento: Artigo
Idioma: por
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/47753
Resumo: Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Genética Bioquímica. Belo Horizonte, MG, Brasil.
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spelling Costa-Silva, Héllida MarinaResende, Bruno CarvalhoUmaki, Adriana Castilhos SouzaPrado, WillianSilva, Marcelo Santos daVirgílio, StelaMacedo, Andrea MaraPena, Sérgio Danilo JunhoTahara, Erich BirelliTosi, Luiz Ricardo OrsiniElias, Maria CarolinaAndrade, Luciana OliveiraReis-Cunha, João LuísFranco, Glória ReginaFragoso, Stenio PerdigãoMachado, Carlos Renato2021-06-17T18:41:25Z2021-06-17T18:41:25Z2021COSTA-SILVA, Héllida Marina et al. DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi. Frontiers in Cell and Developmental Biology, v. 9, p. 1–22, 2021.2296-634Xhttps://www.arca.fiocruz.br/handle/icict/4775310.3389/fcell.2021.633195porFrontiers MediaDNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruziinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Genética Bioquímica. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Genética Bioquímica. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Molecular e Sistêmica de Tripanossomatídeos. Curitiba, PR, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Genética Bioquímica. Belo Horizonte, MG, Brasil.Instituto Butantan. Centro de Toxinas, Resposta-imune e Sinalização Celular. Laboratório de Ciclo Celular. Butantã, SP, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos. Laboratório de Biologia Molecular de Leishmanias. Ribeirão Preto, SP, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Genética Bioquímica. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Genética Bioquímica. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Genética Bioquímica. Belo Horizonte, MG, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos. Laboratório de Biologia Molecular de Leishmanias. Ribeirão Preto, SP, Brasil.Instituto Butantan. Centro de Toxinas, Resposta-imune e Sinalização Celular. Laboratório de Ciclo Celular. Butantã, SP, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Laboratório de Biologia Celular e Molecular. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Escola de Veterinária. Departamento de Medicina Veterinária. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Genética Bioquímica. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Molecular e Sistêmica de Tripanossomatídeos. Curitiba, PR, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Genética Bioquímica. Belo Horizonte, MG, Brasil.DNA topoisomerases are enzymes that modulate DNA topology. Among them, topoisomerase 3α is engaged in genomic maintenance acting in DNA replication termination, sister chromatid separation, and dissolution of recombination intermediates. To evaluate the role of this enzyme in Trypanosoma cruzi, the etiologic agent of Chagas disease, a topoisomerase 3α knockout parasite (TcTopo3α KO) was generated, and the parasite growth, as well as its response to several DNA damage agents, were evaluated. There was no growth alteration caused by the TcTopo3α knockout in epimastigote forms, but a higher dormancy rate was observed. TcTopo3α KO trypomastigote forms displayed reduced invasion rates in LLC-MK2 cells when compared with the wild-type lineage. Amastigote proliferation was also compromised in the TcTopo3α KO, and a higher number of dormant cells was observed. Additionally, TcTopo3α KO epimastigotes were not able to recover cell growth after gamma radiation exposure, suggesting the involvement of topoisomerase 3α in homologous recombination. These parasites were also sensitive to drugs that generate replication stress, such as cisplatin (Cis), hydroxyurea (HU), and methyl methanesulfonate (MMS). In response to HU and Cis treatments, TcTopo3α KO parasites showed a slower cell growth and was not able to efficiently repair the DNA damage induced by these genotoxic agents. The cell growth phenotype observed after MMS treatment was similar to that observed after gamma radiation, although there were fewer dormant cells after MMS exposure. TcTopo3α KO parasites showed a population with sub-G1 DNA content and strong γH2A signal 48 h after MMS treatment. So, it is possible that DNA-damaged cell proliferation due to the absence of TcTopo3α leads to cell death. Whole genome sequencing of MMS-treated parasites showed a significant reduction in the content of the multigene families DFG-1 and RHS, and also a possible erosion of the sub-telomeric region from chromosome 22, relative to non-treated knockout parasites. Southern blot experiments suggest telomere shortening, which could indicate genomic instability in TcTopo3α KO cells owing to MMS treatment. Thus, topoisomerase 3α is important for homologous recombination repair and replication stress in T. cruzi, even though all the pathways in which this enzyme participates during the replication stress response remains elusive.DNA topoisomerase 3αHomologous RecombinationDNA DamageDNA RepairADN-TopoisomerasasRecombinación HomólogaDaño del ADNReparación del ADNADN topoisomérasesAltération de l'ADNRéparation de l'ADNDNA TopoisomerasesRecombinação HomólogaTrypanosoma cruziDano ao DNAReparo do DNAinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi
title DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi
spellingShingle DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi
Costa-Silva, Héllida Marina
DNA topoisomerase 3α
Homologous Recombination
DNA Damage
DNA Repair
ADN-Topoisomerasas
Recombinación Homóloga
Daño del ADN
Reparación del ADN
ADN topoisomérases
Altération de l'ADN
Réparation de l'ADN
DNA Topoisomerases
Recombinação Homóloga
Trypanosoma cruzi
Dano ao DNA
Reparo do DNA
title_short DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi
title_full DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi
title_fullStr DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi
title_full_unstemmed DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi
title_sort DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi
author Costa-Silva, Héllida Marina
author_facet Costa-Silva, Héllida Marina
Resende, Bruno Carvalho
Umaki, Adriana Castilhos Souza
Prado, Willian
Silva, Marcelo Santos da
Virgílio, Stela
Macedo, Andrea Mara
Pena, Sérgio Danilo Junho
Tahara, Erich Birelli
Tosi, Luiz Ricardo Orsini
Elias, Maria Carolina
Andrade, Luciana Oliveira
Reis-Cunha, João Luís
Franco, Glória Regina
Fragoso, Stenio Perdigão
Machado, Carlos Renato
author_role author
author2 Resende, Bruno Carvalho
Umaki, Adriana Castilhos Souza
Prado, Willian
Silva, Marcelo Santos da
Virgílio, Stela
Macedo, Andrea Mara
Pena, Sérgio Danilo Junho
Tahara, Erich Birelli
Tosi, Luiz Ricardo Orsini
Elias, Maria Carolina
Andrade, Luciana Oliveira
Reis-Cunha, João Luís
Franco, Glória Regina
Fragoso, Stenio Perdigão
Machado, Carlos Renato
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Costa-Silva, Héllida Marina
Resende, Bruno Carvalho
Umaki, Adriana Castilhos Souza
Prado, Willian
Silva, Marcelo Santos da
Virgílio, Stela
Macedo, Andrea Mara
Pena, Sérgio Danilo Junho
Tahara, Erich Birelli
Tosi, Luiz Ricardo Orsini
Elias, Maria Carolina
Andrade, Luciana Oliveira
Reis-Cunha, João Luís
Franco, Glória Regina
Fragoso, Stenio Perdigão
Machado, Carlos Renato
dc.subject.en.pt_BR.fl_str_mv DNA topoisomerase 3α
Homologous Recombination
DNA Damage
DNA Repair
topic DNA topoisomerase 3α
Homologous Recombination
DNA Damage
DNA Repair
ADN-Topoisomerasas
Recombinación Homóloga
Daño del ADN
Reparación del ADN
ADN topoisomérases
Altération de l'ADN
Réparation de l'ADN
DNA Topoisomerases
Recombinação Homóloga
Trypanosoma cruzi
Dano ao DNA
Reparo do DNA
dc.subject.es.pt_BR.fl_str_mv ADN-Topoisomerasas
Recombinación Homóloga
Daño del ADN
Reparación del ADN
dc.subject.fr.pt_BR.fl_str_mv ADN topoisomérases
Altération de l'ADN
Réparation de l'ADN
dc.subject.decs.pt_BR.fl_str_mv DNA Topoisomerases
Recombinação Homóloga
Trypanosoma cruzi
Dano ao DNA
Reparo do DNA
description Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Genética Bioquímica. Belo Horizonte, MG, Brasil.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-06-17T18:41:25Z
dc.date.available.fl_str_mv 2021-06-17T18:41:25Z
dc.date.issued.fl_str_mv 2021
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv COSTA-SILVA, Héllida Marina et al. DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi. Frontiers in Cell and Developmental Biology, v. 9, p. 1–22, 2021.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/47753
dc.identifier.issn.pt_BR.fl_str_mv 2296-634X
dc.identifier.doi.none.fl_str_mv 10.3389/fcell.2021.633195
identifier_str_mv COSTA-SILVA, Héllida Marina et al. DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi. Frontiers in Cell and Developmental Biology, v. 9, p. 1–22, 2021.
2296-634X
10.3389/fcell.2021.633195
url https://www.arca.fiocruz.br/handle/icict/47753
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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https://www.arca.fiocruz.br/bitstream/icict/47753/3/fcell-09-63319ok.pdf.txt
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