7 General and Pathway-specific Regulatory Mechanisms Controlling the Synthesis of Amino Acid Biosynthetic Enzymes in Saccharomyces cerevisiae

I. INTRODUCTION The regulation of genes encoding amino acid biosynthetic enzymes in Saccharomyces cerevisiae involves a complex interplay between numerous control mechanisms. Most of these genes are subject to a cross-pathway regulatory system known as general amino acid control that increases their expression under conditions of amino acid starvation. Gcn4p is the direct positive regulator of gene expression in this system. Additional regulatory elements are required for efficient basal expression during growth in minimal medium, and in one case, the basal control element functions in a second cross-pathway regulatory system that responds to the level of inorganic phosphate in the medium. In addition to these mechanisms, many amino acid biosynthetic genes are subject to pathway-specific controls that reduce enzyme expression when the amino acid endproduct of the pathway is present in the medium. In some instances, pathway-specific repression can override derepression by Gcn4p under starvation conditions in which the endproduct of that particular pathway is not limiting. Thus, the existence of pathway-specific regulation can sometimes make it difficult to determine whether or not a given gene is subject to general amino acid control. In this chapter, the regulatory elements involved in determining basal expression and general amino acid control are discussed first, followed by a description of pathway-specific repression mechanisms and the interplay between cross-pathway and amino-acid-specific controls. Regulatory mechanisms that modulate enzyme activity rather than enzyme synthesis, such as endproduct inhibition, are not discussed in this chapter; for a thorough review of this topic, see Jones and Fink (1982).