Replication Protein A presents canonical functions and is also involved in the differentiation capacity of Trypanosoma cruzi

dc.creatorPavani, Raphel Souza
dc.creatorSilva, Marcelo Santos da
dc.creatorFernandes, Carlos Alexandre Henrique
dc.creatorMorini, Flavia Souza
dc.creatorAraujo, Christiane Bezerra
dc.creatorFontes, Marcos Roberto de Mattos
dc.creatorSant'anna, Osvaldo Augusto
dc.creatorMachado, Carlos Renato
dc.creatorCano, Maria Isabel
dc.creatorFragoso, Stenio Perdigão
dc.creatorElias, Maria Carolina Quartim Barbosa
dc.date2017-07-26T11:56:07Z
dc.date2017-07-26T11:56:07Z
dc.date2016
dc.date.accessioned2023-09-26T21:59:02Z
dc.date.available2023-09-26T21:59:02Z
dc.identifierPAVANI, Raphael Souza et al. Replication Protein A presents canonical functions and is also involved in the differentiation capacity of Trypanosoma cruzi. PLoS Negl. Trop. Dis., v. 10, n. 12, p. 1-28, Dec. 2016.
dc.identifier1935-2735
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/20407
dc.identifier10.1371/journal.pntd.0005181
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8874265
dc.descriptionReplication Protein A (RPA), the major single stranded DNA binding protein in eukaryotes, is composed of three subunits and is a fundamental player in DNA metabolism, participating in replication, transcription, repair, and the DNA damage response. In human pathogenic trypanosomatids, only limited studies have been performed on RPA-1 from Leishmania. Here, we performed in silico, in vitro and in vivo analysis of Trypanosoma cruzi RPA-1 and RPA-2 subunits. Although computational analysis suggests similarities in DNA binding and Ob-fold structures of RPA from T. cruzi compared with mammalian and fungi RPA, the predicted tridimensional structures of T. cruzi RPA-1 and RPA-2 indicated that these molecules present a more flexible tertiary structure, suggesting that T. cruzi RPA could be involved in additional responses. Here, we demonstrate experimentally that the T. cruzi RPA complex interacts with DNA via RPA-1 and is directly related to canonical functions, such as DNA replication and DNA damage response. Accordingly, a reduction of TcRPA-2 expression by generating heterozygous knockout cells impaired cell growth, slowing down S-phase progression. Moreover, heterozygous knockout cells presented a better efficiency in differentiation from epimastigote to metacyclic trypomastigote forms and metacyclic trypomastigote infection. Taken together, these findings indicate the involvement of TcRPA in the metacyclogenesis process and suggest that a delay in cell cycle progression could be linked with differentiation in T. cruzi.
dc.formatapplication/pdf
dc.languageeng
dc.publisherInstituto de Investigaciones Biotecnológicas
dc.rightsopen access
dc.subjectTrypanosoma cruzi
dc.subjectDNA Replication
dc.subjectStaphylococcal Protein A
dc.subjectReplicación del ADN
dc.subjectProteína Estafilocócica A
dc.subjectReplicação do DNA
dc.subjectProteína Estafilocócica A
dc.titleReplication Protein A presents canonical functions and is also involved in the differentiation capacity of Trypanosoma cruzi
dc.typeArticle


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