A mutation of Saccharomyces cerevisiae leading to resistance to some inhibitors of peptide bond formation

Abstract

A mutant of the yeast Saccharomyces cerevisiae has been isolated that is resistant to narciclasine, an inhibitor of peptide bond formation on 80S ribsomes. The mutant shows cross-resistance to a number of inhibitors of peptidyl transferase including anthelmycin, a 4-aminohexosyl cytosine antibiotic, which does not compete with narciclasine for its ribosomal binding site. The mutation is within the gene tcm1 or a closely linked gene on chromosome XV; it is expressed in the 60S ribosomal subunit. The parameters of the binding of (3H)narciclasine to ribosomes and ribosomal subunits from both wild-type and mutant strains have been calculated by ultracentrifugation. One molecule of narciclasine is bound per ribosome or per 60S ribosomal subunit, the values of the dissociation constants being 0.054 and 0.13 μm respectively, for 80S and 60S particles from the wild-type cells. Ribosomes of the mutant strain have a lower affinity for narciclasine and trichodermin than ribosomes from wild-type cells. The mutation is semidominant in heterozygous diploid cells.