Identification and Characterization of Sir2 Inhibitors Through Phenotypic Assays in Yeast

Title: Identification and Characterization of Sir2 Inhibitors Through Phenotypic Assays in Yeast

Volume: 7 Issue: 7

Author(s): Jeff Posakony, Maki Hirao and Antonio Bedalov

Affiliation:

Keywords: deacetylase inhibitors, sir2 inhibitors, yeast-based phenotypic assays, splitomicin

Abstract: Yeast Sir2 is a defining member of a large family of protein deacetylases found in organisms ranging from bacteria to humans. SIR2 was discovered as a gene required for mating in S. cerevisiae 25 years ago, but it was only recently that Sir2s activity as an NAD-dependent protein deacetylase was established. However, years of extensive research did generate a large body of knowledge about the cellular roles of Sir2 in yeast long before its biochemical function was discovered. In addition to Sir2, yeast have four additional NAD-dependent histone deacetylases Hst1-4 (for homologue of Sir2), with distinct cellular roles. Detailed knowledge of the phenotypes of SIR2 and HST loss of function mutants has allowed design of a series of cell based screens that yielded the first inhibitors of NAD-dependent protein deacetylases. These phenotypic assays, amenable to high throughput screening, and coupled with transcript array analysis for evaluation of compound specificity, allowed the identification and detailed characterization of a series of Sir2 inhibitors, entirely bypassing traditional biochemical approaches.XXXY YYZZZ

Cite this article as:

Posakony Jeff, Hirao Maki and Bedalov Antonio, Identification and Characterization of Sir2 Inhibitors Through Phenotypic Assays in Yeast, Combinatorial Chemistry & High Throughput Screening 2004; 7 (7) . https://dx.doi.org/10.2174/1386207043328346