AMILORIDE TOXICITY IN THE FISSION YEAST SCHIZOSACCHAROMYCES-POMBE IS RELEASED BY THIAMINE AND MUTATIONS IN THE THIAMINE-REPRESSIBLE GENE CAR1

Amiloride (Am) inhibits growth in the fission yeast Schizosaccharomyce s pombe. We show that the toxic effect of this drug is relieved by low concentrations of thiamine (Th) and that the pyrimidine moiety of the Th molecule is responsible for growth inhibition release. A putative membrane protein encoded by the carl gene is the target for Am action. It is responsible for Am sensitivity and is involved in the utilizati on of Th and its biosynthetic precursor, 4-amino-5-hydroxy-methyl-2-me thylpyrimidine. Its expression is repressed by Th and is under the gen etic control of the genes, thi1, tnr1, tnr2 and tnr3, which have previ ously been shown to be responsible for the transcriptional control of genes involved in the biosynthesis and dephosphorylation of Th.