| Full text | |
| Author(s): Show less - |
Pavani, Raphael Souza
;
da Silva, Marcelo Santos
;
Henrique Fernandes, Carlos Alexandre
;
Morini, Flavia Souza
;
Araujo, Christiane Bezerra
;
de Mattos Fontes, Marcos Roberto
;
Sant'Anna, Osvaldo Augusto
;
Machado, Carlos Renato
;
Cano, Maria Isabel
;
Fragoso, Stenio Perdigao
;
Elias, Maria Carolina
Total Authors: 11
|
| Document type: | Journal article |
| Source: | PLoS Neglected Tropical Diseases; v. 10, n. 12 DEC 2016. |
| Web of Science Citations: | 5 |
| Abstract | |
Replication 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. (AU) | |
| FAPESP's process: | 14/13375-5 - Replication origins in trypanosomes |
| Grantee: | Christiane Bezerra de Araujo |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 14/24170-5 - DNA replication dynamics in Trypanosoma cruzi: licensing and replication rate characterization |
| Grantee: | Marcelo Santos da Silva |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 13/17864-8 - Structural Studies with Neurotoxic Phospholipases A2. |
| Grantee: | Carlos Alexandre Henrique Fernandes |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 14/02978-0 - Functional analysis of RPA complex in Trypanosoma cruzi and its involvement with telomeric DNA |
| Grantee: | Raphael Souza Pavani |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling |
| Grantee: | Hugo Aguirre Armelin |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 15/10580-0 - Characterization of intra-S checkpoint in Trypanosoma cells |
| Grantee: | Maria Carolina Quartim Barbosa Elias Sabbaga |
| Support Opportunities: | Regular Research Grants |