Screening of bio-active substances by using a peculiar phenotype of yeast mutant

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An inappropriate activation of a signaling pathway in yeast often has a deleterious physiological effect and causes various defects, including growth defects. In a certain genetic background (Δzdsl) of Saccharomyces cerevisiae, the cell-cycle progression in G2 is specifically blocked in the medium with CaCl_2 by the hyperactivation of the Ca^<2+>-signaling pathways. Here, we developed a novel drug screening procedure designed to detect the active compounds that specifically attenuate the Ca^<2+>-signaling activity on the basis of the ability to abrogate the growth defect of the cells suffering from the hyperactivated Ca^<2+> signal. Using known calcineurin inhibitors as model compounds, we have established the screening conditions for the drugs that suppress the Ca^<2+>-induced growth inhibition. An indicator strain with an increased drug sensitivity was constructed with a syr1/erg3 null mutation.