title: Caffeine-resistance in fission yeast is caused by mutations in a single essential gene, crm1+.
abstract: Caffeine is a base analogue and is known to affect a wide variety of cellular processes. In order to dissect genetically molecules which mediate the biological effects of caffeine, temperature-sensitive (ts) and caffeine-resistant mutants were isolated from fission yeast, Schizosaccharomyces pombe. Surprisingly, all twelve ts isolates contained a mutation in the same locus, crm1. Cells of the ts crm1 mutant showed an abnormal chromosome structure at the restrictive temperature, an elevated expression of Pap1-dependent transcription, and cross-resistance to an unrelated drug such as staurosporine. Overproduction of pap1+ also conferred caffeine resistance, whilst the resistance of the crm1 mutant is abolished in the pap1- background. These results show that the crm1+ gene is a major locus for caffeine resistance, which arises from Pap1-dependent transcriptional activation.
authors.affiliation: Department of Biophysics, Faculty of Science, Kyoto University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kumada
authors.forename: M
authors.initials: M
authors.lastname: Yanagida
authors.forename: T
authors.initials: T
authors.lastname: Toda
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000483:Alleles; D026905:Amino Acid Transport Systems; D050976:Basic-Leucine Zipper Transcription Factors; D002110:Caffeine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D028884:Karyopherins; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D000073718:Pancreatitis-Associated Proteins; D010641:Phenotype; D011062:Polynucleotide Adenylyltransferase; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D019311:Staurosporine; D013696:Temperature; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D000097606:Exportin 1 Protein
chemical_list: D000470:Alkaloids; D026905:Amino Acid Transport Systems; D050976:Basic-Leucine Zipper Transcription Factors; D002110:Caffeine; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; D005656:Fungal Proteins; D028884:Karyopherins; D008565:Membrane Proteins; D000073718:Pancreatitis-Associated Proteins; D011062:Polynucleotide Adenylyltransferase; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D019311:Staurosporine; D015534:Trans-Activators; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C429560:BAP3 protein, S cerevisiae; C105096:Pap1 protein, S pombe; C000612141:REG3A protein, human; C093857:rpn11 protein, S pombe; C429559:PAP1 protein, S cerevisiae; C038753:leptomycin B