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 Schizosaccharomyces 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 car1 gene is the target for Am action. It is responsible for Am sensitivity and is involved in the utilization of Th and its biosynthetic precursor, 4-amino-5-hydroxymethyl-2-methylpyrimidine. Its expression is repressed by Th and is under the genetic control of the genes, thi1, tnr1, tnr2 and tnr3, which have previously been shown to be responsible for the transcriptional control of genes involved in the biosynthesis and dephosphorylation of Th.
Niederberger
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Institute of General Microbiology, University of Bern, Switzerland.
Fankhauser
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Edenharter
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Schweingruber
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ME
D000584:Amiloride / Q000494:pharmacology*; D000963:Antimetabolites / Q000494:pharmacology; D001119:Arginase / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009154:Mutation / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology; D011745:Pyrithiamine / Q000494:pharmacology; D012331:RNA, Fungal / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins; D013831:Thiamine / Q000378:metabolism* / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000963:Antimetabolites; D005656:Fungal Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D011743:Pyrimidines; D012331:RNA, Fungal; D012333:RNA, Messenger; D029702:Schizosaccharomyces pombe Proteins; D013844:Thiazoles; C490026:bsu1 protein, S pombe; C012572:2-(4-methyl-1,3-thiazol-5-yl)ethanol; D011745:Pyrithiamine; D000584:Amiloride; D001119:Arginase; D013831:Thiamine