PRS1 IS A KEY MEMBER OF THE GENE FAMILY ENCODING PHOSPHORIBOSYLPYROPHOSPHATE SYNTHETASE IN SACCHAROMYCES-CEREVISIAE

In Saccharomyces cerevisiae the metabolite phosphoribosyl-pyrophosphat e (PRPP) is required for purine, pyrimidine, tryptophan and histidine biosynthesis. Enzymes that can synthesize PRPP can be encoded by at le ast four genes. We have studied 5-phospho-ribosyl-1(alpha)-pyrophospha te synthetases (PRS) genetically and biochemically. Each of the four g enes, all of which are transcribed, has been disrupted in haploid yeas t strains of each mating type and although all disruptants are able to grow on complete medium, differences in growth rate and enzyme activi ty suggest that disruption of PRS1 or PRS3 has a significant effect on cell metabolism, whereas disruption of PRS2 or PRS4 has little measur able effect. Using Western blot analysis with antisera raised against peptides derived from the non-homology region (NHR) and the N-terminal half of the PAS1 gene product it has been shown that the NHR is not r emoved by protein splicing. However, the fact that disruption of this gene causes the most dramatic decrease in cell growth rate and enzyme activity suggests that Prs1p may have a key structural or regulatory r ole in the production of PRPP in the cell.