REGULATION OF THE PYRIMIDINE SALVAGE PATHWAY BY THE FUR1 GENE-PRODUCT OF SACCHAROMYCES-CEREVISIAE

In Saccharomyces cerevisiae, the protein encoded by the FUR1 gene is absolutely required for the expression of uracil phosphoribosyl transferase activity. The occurrence of semi-dominant mutations for 5-fluorouracil-( 5FU)-resistance at this locus led us to clone and sequence the semi-dominant fur1-5 allele. A single point mutation, resulting in the substitution of arginine 134 for serine, is responsible for this mutant phenotype. The fur1-5 allele is transcribed and expressed at the same level as the wild-type allele. But, in contrast with the wild-type, the UPRTase activity of the fur1-5 mutant strain is stimulated in vitro by UTP and does not, therefore, correspond to a loss of feedback of UPRTase activity. We found that uracil, as a free base, induces a significative increase in transcription and UPRTase activity in a wild-type strain as well as in uracil-overproducing mutants which principally explains the high efficiency of the pyrimidine salvage pathway in S. cerevisiae.