Regulatory Circuits for Gene Expression: The Metabolism of Galactose and Phosphate

INTRODUCTION The enzyme system responsible for the initial steps of galactose utilization offers considerable advantages over other systems in the study of genetic regulatory mechanisms involved in enzyme synthesis in Saccharomyces cerevisiae. One advantage is that the synthesis of these enzymes is regulated in response to a simple external effector, galactose as inducer, whereas the activities are affected by carbon catabolite repression and inhibition. In practice, there are neither inherently programmed control mechanisms, like the master timing mechanism suggested in the cell-division cycle (Hartwell et al. 1974), nor complex interactions between various effectors or between different enzyme proteins, like those in the regulation of some biosynthetic pathway enzymes in microorganisms (Calvo and Fink 1971; Metzenberg 1979). Likewise, the galactose system does not involve duplicated genes for a particular gene function, which is common in maltose and sucrose utilization (Mortimer and Hawthorne 1969), nor housekeeping enzymes like those observed in acid and alkaline phosphatases in Neurospora crassa (Metzenberg 1979) and S. cerevisiae (Toh-e et al. 1973Toh-e et al. 1976). Having these advantages, the galactose system has been subjected to intensive genetic analysis, and a model of genetic regulation has been proposed by Douglas and Hawthorne (1966). This provided an initial clue to the understanding of one genetic regulatory mechanism in yeast. Also under investigation in our laboratory is the system regulating the synthesis of phosphatases in S. cerevisiae. Although this system involves housekeeping enzymes, most of the activities are due to the repressible enzymes; their activities are controlled in response to a simple...