Suppression of the Saccharomyces cerevisiae hac1/ire15 mutation by yeast genes and human cDNAs

We previously reported that the Saccharomyces cerevisiae ire15 mutation results in an inositol-auxotrophic phenotype, and that human cDNAs can suppress the ire15 mutation (Nikawa, J., 1994. A cDNA encoding the human transforming growth factor beta receptor suppresses the growth defect of a yeast mutant. Gene 149, 367-372; Nikawa, J., Nakano, H., Ohi, N., 1996b. Structural and functional conservation of human and yeast HACl genes which can suppress the growth defect of the Saccharomyces cerevisiae ire15 mutant. Gene 171, 107-111). Herein, we present evidence that the gene responsible for the ire15 mutation is HACl, which encodes a transcription factor for KAR2, obtained by isolating a yeast single-copy suppressor gene and by performing complementation analysis. Sequencing analysis revealed that the mutant HACl gene obtained from the ire15 mutant contained an AAA codon at position 50 instead of the AGA codon observed in the wild-type gene, resulting in the alteration of the aa from Arg to Lys. All human cDNAs and yeast multicopy suppressors, which had been isolated as suppressors for the ire15 mutation, were able to suppress the inositol-auxotrophic phenotype but not the defect in KAR2 induction of the had-disrupted strain. (C) 1997 Elsevier Science B.V.