| Grant number: | 14/02978-0 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Effective date (Start): | April 01, 2015 |
| Effective date (End): | March 31, 2019 |
| Field of knowledge: | Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms |
| Acordo de Cooperação: | Coordination of Improvement of Higher Education Personnel (CAPES) |
| Principal Investigator: | Maria Carolina Quartim Barbosa Elias Sabbaga |
| Grantee: | Raphael Souza Pavani |
| Host Institution: | Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
| Associated research grant: | 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID |
| Associated scholarship(s): | 16/24255-6 - Defining post-translational modifications and interactors for Replication Protein A (RPA) from trypanosomatids associated with DNA damage., BE.EP.DR |
Abstract Chagas disease is caused by the protozoan Trypanosoma cruzi, afflicting several regions ofworld, with a primary focus in Latin America. Despite advances, approximately eight million people are infected with this disease. The study of the molecular biology of this parasite may facilitate the discovery of new therapies as well as assist in understanding the molecular evolution of eukaryotic organisms. The telomeric complex, responsible for the integrity and genomic stability, is formed by the interaction of DNA with proteins that are responsible for maintaining and protecting these terminals. The RPA complex in eukaryotes comprises a heterotrimer that participates in replication, repair, recombination and telomere maintenance. In mammals and yeast, the RPA complex is mainly involved with replication and repair in telomeres. Studies conducted by our group showed that RPA - 1 of T. cruzi interacts with telomeres in vivo in replicative and non-replicative forms and showed that, unlike other organisms, this protein has affinity for G -rich telomeric strand. Furthermore, structural analysis of RPA -1 protein shows significant differences when compared with RPA -1 from higher eukaryotes, such as the absence of 70N domain that interacts with repair machinery proteins. In Leishmania amazonensis, only RPA - 1 subunit was found interacting with telomeres. The absence of homologous proteins that interact with the telomere overhang on trypanosomes, specific interaction RPA -1- telomere, structural peculiarities of tripanossomatids RPA lead us to hypothesize that this protein plays a distinct role on the telomeres of this parasites, maybe involved in protection of telomeres. This project aims to understand the role of the RPA complex at the telomeres through experiments of RNAi silencing of RPA-1 and through complementation assay in yeasts. It also aims to initiate studies with the RPA - 2, to check the occurrence of the RPA trimerization in telomere, as well as new search for proteins that interacts with the complex performing immunoprecipitation assays, followed by mass spectrometry analysis. (AU) | |
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