Cordycepin in Schizosaccharomyces pombe: effects on the wild type and phenotypes of mutants resistant to the drug.

The adenosine analogue cordycepin (3'-deoxyadenosine) inhibits growth and causes aberrant cell morphology in the fission yeast, Schizosaccharomyces pombe. Exogenously added thiamine, the pyrimidine moiety of the thiamine molecule, and adenine alleviate its growth-disturbing effect. At concentrations that do not inhibit growth, the drug reduces mating and sporulation and causes a decrease in the mRNA level of gene ste11 and the ste11-dependent gene, mei2. The mating- and sporulation-inhibiting effect of cordycepin is overcome by adenine. A mutant disrupted for the ado1 gene encoding adenosine kinase exhibits a cordycepin-resistant and methionine-sensitive phenotype, excretes adenosine into the medium and mates and sporulates poorly in the presence of adenine. A S. pombe mutant containing a frameshift mutation at the beginning of the carboxy-terminal half of gene ufd1 (the Saccharomyces cerevisiae UFD1 homologue) is cordycepin-resistant and sterile. Strains disrupted for the ufd1 gene only form microcolonies.