Role of phosphorylation of Orc1Cdc6 protein in the cell cycle of Trypanosoma cruzi

• Grant number: 23/00557-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2023
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Maria Carolina Quartim Barbosa Elias Sabbaga
• Grantee: Melissa Martins de Oliveira
• 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

The DNA replication process during the cell cycle requires strict control to ensure genomic stability. In most eukaryotes, this process begins with the pre-replication complex (pre-RC) composed by the ORC hexamer and the Cdc6 and Cdt1 proteins, which associate with the DNA to allow the recruitment of the MCM complex, which has helicase activity, initiating the process of DNA denaturation. The replication process of Trypanosoma cruzi, the etiologic agent of Chagas' disease, is not well-known: for example, the mechanisms that activate replication during the S phase are unknown. This organism has a protein, homologous to Orc1 and Cdc6 and named Orc1Cdc6, composing the pre-RC. Orc1Cdc6 is present in the nuclear space at all stages of the T. cruzi cell cycle. Preliminary data from our group suggested phosphorylation of Orc1Cdc6 in the epimastigote form of T. cruzi, and thus, we hypothesize that this/these phosphorylation(s) is(are) involved in the modulation of replication that occurs during S phase. Therefore, the project aims to (i) identify these phosphorylations and (ii) assess whether they are involved in the modulation of replication that occurs during the cell cycle of T. cruzi.