Overlapping functions of the yeast oxysterol-binding protein homologues

The Saccharomyces cerevisiae genome encodes seven homologues of the mammali an oxysterol-binding protein (OSBP), a protein implicated in lipid traffick ing and sterol homeostasis. To determine the functions of the yeast OSBP ge ne family (OSH1-OSH7), we used a combination of genetics, genomics, and ste rol lipid analysis to characterize OSH deletion mutants. All 127 combinatio ns and permutations of OSH deletion alleles were constructed. Individual OS H genes were not essential for yeast viability, but the elimination of the entire gene family was lethal. Thus, the family members shared an essential function. In addition, the in vivo depletion of all Osh proteins disrupted sterol homeostasis. Like mutants that affect ergosterol production, the vi able combinations of OSH deletion alleles exhibited specific sterol-related defects. Although none of the single OSH deletion mutants was defective fo r growth, gene expression profiles revealed that each mutant had a characte ristic molecular phenotype. Therefore, each gene performed distinct nonesse ntial functions and contributed to a common essential function. Our finding s indicated that OSH genes performed a multitude of nonessential roles defi ned by specific subsets of the genes and that most shared at least one esse ntial role potentially linked to changes in sterol lipid levels.