Caffeine-resistance in fission yeast is caused by mutations in a single essential gene, crm1⁺

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 crml 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 papl^- background. These results show that the crml⁺ gene is a major locus for caffeine resistance, which arises from Pap1-dependent transcriptional activation.