Investigation of the mechanism of nucleus-cytoplasm RPA transport

• Grant number: 21/12872-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: February 01, 2022
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Maria Carolina Quartim Barbosa Elias Sabbaga
• Grantee: Giovanna Nalin Parmegiani
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 20/00694-6 - How DNA replication contributes for the success of infection caused by Trypanosoma cruzi, AP.TEM

Abstract

Replication Protein A (RPA), the main single-stranded DNA ligand of eukaryotes, is a heterotrimeric complex formed by three subunits (RPA-1, RPA2 and RPA-3) and participates in several fundamental processes such as replication, repair and signaling checkpoint. Our group found that, depending on the life form of the parasite, RPA is found in the nucleus (in replicative forms) or in the cytoplasm (in infective forms). We also showed that the export of RPA is essential for the process of differentiating from replicative to infective forms, as mutations in three of the ten aminoacids that form the NES (Nuclear Export Signal, present in the RPA-2 subunit in trypanosomatids) block 100% of the differentiation of epimastigote forms into metacyclic trypomastigotes, raising the suspicion that this process may strongly contribute to blocking replication in infective forms. This project aims to identify the exportin responsible for the nucleus-cytoplasm transport of RPA and the molecular modulation (possibly via sumoylation) of this transport. (AU)