Exploring the Roles of Lysine Deacetylases in Saccharomyces cerevisiae

• Main Author: Kaluarachchi, Supipi Wasana Kumari
• Other Authors: Andrews, Brenda
• Language: en_ca
• Published: 2011
• Subjects: Cell cycle; Lysine Deacetylase; Functional Genomics; 0369; 0307
• Online Access: http://hdl.handle.net/1807/32071

This work investigates two distinct roles of lysine deacetylases (KDACs) in the budding yeast Saccharomyces cerevisiae. The first part focused on the classical, well characterized role of KDACs as transcriptional regulators and deciphering their role in G1 transcription. I show that two yeast KDACs, Rpd3 and Hos3 are recruited to G1 promoters through their interactions with the negative regulator Whi5 and that these KDACs are necessary for proper Whi5-mediated repression. The second part examines a newly discovered role for KDACs extending their role beyond the chromatin as modifiers of proteins other than the histones. I present here the first systematic approach that comprehensively examines these non-histone targets of KDACs in vivo. I identified 73 non-histone proteins acetylated in vivo involved in diverse cellular processes. Swi4, a component of the G1 transcription factor SBF, was identified in the Rpd3 screen and I show that the interaction between Swi4 and its heterodimeric partner Swi6 was regulated by acetylation. My findings significantly expand the scope of the yeast acetylome and demonstrate the utility of systematic functional genomic screens to explore enzymatic pathways.