Chemical-genetic profile analysis of five inhibitory compounds in yeast

Colony size reduction was used to investigate the chemical-genetic profile of cycloheximide, 3-amino-1,2,4-triazole, paromomycin, streptomycin and neomycin in the yeast Saccharomyces cerevisiae. These compounds target the process of protein biosynthesis. More than 70,000 strains were analyzed from the array of gene deletion mutant yeast strains. As expected, the overall profiles of the tested compounds were similar, with deletions for genes involved in protein biosynthesis being the major category followed by metabolism. This implies that novel genes involved in protein biosynthesis could be identified from these profiles. Further investigations were carried out to assess the activity of three profiled genes in the process of protein biosynthesis using relative fitness of double mutants and other genetic assays.Chemical-genetic profiles provide insight into the molecular mechanism(s) of the examined compounds by elucidating their potential primary and secondary cellular target sites. Our follow-up investigations into the activity of three profiled genes in the process of protein biosynthesis provided further evidence concerning the usefulness of chemical-genetic analyses for annotating gene functions. We termed these genes TAE2, TAE3 and TAE4 for translation associated elements 2-4.Predicting gene function is a major goal of systems molecular biology in the post genome sequencing era. In this context, the yeast Saccharomyces cerevisiae has emerged as the eukaryotic model organism of choice for large-scale functional genomic investigations. Yeast cells have been subjected to a number of high throughput investigations such as gene expression analysis [1], protein-protein interaction mapping [2,3] and synthetic genetic interaction analysis [4]. Much knowledge relating to the functions of yeast genes has been collated but a significant number of genes are still not characterized in this model organism [5]. Consequently, further studies are required to examine the functi