SACCHAROMYCES-CEREVISIAE MUTANTS SENSITIVE TO THE ANTIMALARIAL AND ANTIARRHYTHMIC DRUG, QUINIDINE

Mutations at three loci in Saccharomyces cerevisiae have been shown to confer increased sensitivity to the antimalarial and antiarrhythmic a lkaloid, quinidine. Two of these groups are composed of strains carryi ng recessive mutations, the other group contains two dominant alleles. The largest complementation group has been designated QDS1, for incre ased quinidine-sensitivity. Exposure of qds1 cells to lethal concentra tions of quinidine results in a novel small-budded terminal morphology in about 70% of the cells in the culture. Strains which carry qds1 al leles share other pleiotropic phenotypes. qds1 mutants are incapable o f mating as alpha but not a cells, due to a defect in alpha-factor pro duction. Homozygous diploid qds1 strains cannot sporulate. Genetic evi dence indicates that QDS1 is allelic to KEX2, a precursor processing p rotease. Loss of QDS1/KEX2 function results in quinidine sensitivity.