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FEBS Lett. 2020 Feb 12. doi: 10.1002/1873-3468.13755. [Epub ahead of print]

Nuclear export of replication protein A in the non-replicative infective forms of Trypanosoma cruzi.

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Laboratório Especial de Ciclo Celular, Instituto Butantan, São Paulo, SP, 05503-900, Brazil.
Center of Toxins, Immune Response and Cell Signaling (CeTICS), Instituto Butantan, São Paulo, SP, 05503-900, Brazil.
Departamento de Física e Biofísica, Instituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Botucatu, SP, 18618-970, Brazil.
Laboratorie de Biologie et Pharmacologie Appliquée, Ecole Normale Supérieure Paris-Saclay, Cachan, France.
Instituto Carlos Chagas, Fiocruz, PR, Brazil.
Laboratório de Parasitologia, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, 05503-900, Brazil.


Replication Protein A (RPA), a heterotrimeric complex, is the major single-stranded DNA-binding protein in eukaryotes. Recently, we characterized RPA from Trypanosoma cruzi, showing that it is involved in DNA replication and DNA damage response in this organism. Better efficiency in differentiation from epimastigote to metacyclic trypomastigote forms was observed in TcRPA-2 subunit heterozygous knockout cells, suggesting that RPA is involved in this process. Here, we show that RPA cellular localization changes during the T. cruzi life cycle, with RPA being detected only in the cytoplasm of the metacyclic and bloodstream trypomastigotes. We also identify a Nuclear Export Signal (NES) in the trypanosomatid RPA-2 subunit. Mutations in the negatively charged residues of RPA-2 NES impair the differentiation process, suggesting that RPA exportation affects parasite differentiation into infective forms.


T. cruzi ; NES; Nuclear Exportation; RPA; Replication Protein A


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