Kumada K, Yanagida M, Toda T
Department of Biophysics, Faculty of Science, Kyoto University, Japan.
Mol Gen Genet. 1996 Jan 15;250(1):59-68. doi: 10.1007/BF02191825.
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.
咖啡因是一种碱基类似物，已知会影响多种细胞过程。为了从基因层面剖析介导咖啡因生物学效应的分子，从裂殖酵母粟酒裂殖酵母中分离出了温度敏感型（ts）和咖啡因抗性突变体。令人惊讶的是，所有12个ts分离株在同一基因座crm1中都含有一个突变。ts crm1突变体的细胞在限制温度下显示出异常的染色体结构、Pap1依赖性转录的表达升高，以及对诸如星形孢菌素等无关药物的交叉抗性。pap1+的过量表达也赋予了咖啡因抗性，而crm1突变体在pap1-背景下的抗性则被消除。这些结果表明，crm1+基因是咖啡因抗性的主要基因座，其源于Pap1依赖性转录激活。
