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

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

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.

Metadados do item

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network_acronym_str	CRUZ
network_name_str	Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str	2135
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)
bitstream.url.fl_str_mv	https://www.arca.fiocruz.br/bitstream/icict/47753/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/47753/2/fcell-09-63319ok.pdf https://www.arca.fiocruz.br/bitstream/icict/47753/3/fcell-09-63319ok.pdf.txt
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repository.name.fl_str_mv	Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv	repositorio.arca@fiocruz.br
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DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi

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