Investigating the Mechanistic Role of the ATR Kinase on the Regulation of the INO80 Chromatin Remodeling Complex in Yeast

Cancer is one of the leading causes of death worldwide, accounting for approximately 10 million deaths in 2020. To better understand cancer, we often look to simpler organisms that share many of the same fundamental biological processes. Yeast serves as an invaluable model organism due to its protein having high conservation with human protein and its great adaptability to outside stressors. This project aims to elucidate how yeast adapt to different nutrient environments. The study focuses on the interaction between Ataxia telangiectasia and Rad3 related (ATR) kinase — known for its crucial role in DNA damage response and metabolic homeostasis — and the INO80 chromatin remodeling complex, investigating ATR and INO80’s roles in cellular adaptation and metabolic regulation under environmental stressors. Since we are working with yeast, Mec1, a yeast homolog of human ATR kinase known for its crucial role in DNA damage response and metabolic homeostasis, will be studied for its regulatory influence on INO80. Through methodologies including yeast transformations and fitness assays across various media, the project seeks to uncover the mechanistic relationship between Mec1 and INO80. Our experiments showed that there are key experimental challenges in reducing Mec1 function in cells, but we did determine genetic interactions between Mec1 and Sml1 in cell viability and identified distinct roles for Rad9, Dun1, and Tel1 in regulating cellular stress adaptation. Understanding how yeast cells cope with stress can shine a light on similar processes in human cells. If we can identify these underlying mechanisms, we might pinpoint new targets for cancer treatments, ultimately helping to manage or even take steps towards preventing the disease.