Investigation of the role of inositol and phosphate metabolism to the maintenance of genomic stability in Saccharomyces cerevisiae

• Grant number: 22/01752-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2022
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: José Renato Rosa Cussiol
• Grantee: Marina Rodrigues Pires
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/05417-0 - DNA damage signaling pathways: mechanisms of regulation and cross-talk with cellular metabolism, AP.JP

Abstract

The response to genomic damage involves several effector proteins that act in many cellular processes promoting adaptations and changes in the organism and its genomes, such as re-establishment of nuclear function (through DNA lesions repair and nuclear proteins) and cellular metabolic reprogramming. Failures to trigger an appropriate cellular response during the genotoxic stress can lead to genomic instability with consequent loss of cellular viability. The inositol metabolism is responsible for the production of a series of molecules such as phospholipids and phosphorylated derivatives of inositol that play essential roles in cellular viability and maintenance. On the other hand, the inorganic phosphate metabolism is responsible to keep the nutritional homeostasis, even in conditions of low nutritional levels. Recent studies have been showing that inositol metabolites are important for DNA Damage Response and that the loss of function of these proteins leads to high sensibility to genotoxins and defects in pathways of DNA damage repair and signaling. Besides that, there are studies showing that the inorganic phosphate metabolism pathway is responsive to genotoxic stress. Therefore, this project aims to study the relevance of inositol metabolism and inorganic phosphate metabolism to genomic instability in eukaryotic cells. Through a combined approach of genomic edition and biochemistry/molecular biology techniques, we will do alterations in these pathways and investigate the cellular impact in DNA damage conditions using Saccharomyces cerevisiae yeast as a model organism.(AU)