Synthetically lethal interactions involving loss of the yeast ERG24: the sterol C-14 reductase gene.

ABSTRACT

ERG2 and ERG24 are yeast sterol biosynthetic genes which are targets of morpholine antifungal compounds. ERG2 and ERG24 encode the C-8 sterol isomerase and the C-14 reductase, respectively. ERG2 is regarded as a non-essential gene but the viability of ERG24 depends on genetic background, type of medium, and CaCl(2) concentration. We demonstrate that erg2 and erg24 mutants are viable in the deletion consortium background but are lethal when combined in the same haploid strain. The erg2erg24 double mutant can be suppressed by mutations in the sphingolipid gene ELO3 but not ELO2. Suppression occurs on rich medium but not on synthetic complete medium. We also demonstrate that the suppressed elo3erg2erg24 does not have a sterol composition markedly different from that of erg24. Further genetic analysis indicates that erg24 combined with mutations in erg6 or erg28 is synthetically lethal but when combined with mutations in erg3 is weakly viable. These results suggest that novel sterol intermediates probably contribute to the synthetic lethality observed in this investigation.