Background: Chemical-genetic profiling of inhibitory compounds can lead to identification of their modes ofaction. These profiles can help elucidate the complex interactions between small bioactive compounds and thecell machinery, and explain putative gene function(s).Results: 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 compoundstarget the process of protein biosynthesis. More than 70,000 strains were analyzed from the array of gene deletionmutant yeast strains. As expected, the overall profiles of the tested compounds were similar, with deletions forgenes involved in protein biosynthesis being the major category followed by metabolism. This implies that novelgenes involved in protein biosynthesis could be identified from these profiles. Further investigations were carriedout to assess the activity of three profiled genes in the process of protein biosynthesis using relative fitness ofdouble mutants and other genetic assays.Conclusion: Chemical-genetic profiles provide insight into the molecular mechanism(s) of the examinedcompounds by elucidating their potential primary and secondary cellular target sites. Our follow-up investigationsinto the activity of three profiled genes in the process of protein biosynthesis provided further evidenceconcerning the usefulness of chemical-genetic analyses for annotating gene functions. We termed these genesTAE2, TAE3 and TAE4 for translation associated elements 2-4.
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