Investigation of the biological role of Opi1, a repressor of inositol metabolism, during the DNA damage response in Saccharomyces cerevisiae

• Grant number: 19/03171-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2019
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: José Renato Rosa Cussiol
• Grantee: Giovanna Marques Panessa
• 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 DNA Damage Response (DDR) is a complex network of biological processes that are activated in response to damages in the DNA molecule, thus preventing genomic instability. The DDR regulates proteins involved in biologic processes such as DNA replication and repair, cell cycle e mitosis being conserved from yeast to humans. Recently, it has been growing evidences suggesting that during the DDR there is an intense metabolic reprogramming of the cell. However, the molecular mechanisms responsible for the cross-talk with the DDR are still to be elucidated. Preliminary data from our group show that budding yeast strains lacking Opi1, a repressor of phospholipid biosynthesis show enhanced sensitivity to the genotoxin MMS, indicating that Opi1 is important for genome maintenance. Although Opi1 is of central importance for the regulation of yeast phospholipid, there is no evidence of its biological role during the DDR. Therefore, we propose through a genetic/biochemical approach to study the biological role of Opi1 during the genotoxic stress induced by MMS. We believe that this project, can contribute to understand how metabolic pathways of the cell, such as inositol metabolism, connects with the DDR.