URA6mutations provide an alternative mechanism for 5-FOA resistance inSaccharomyces cerevisiae

Abstract

AbstractURA3is frequently used in the yeast community as the mutation target for 5-fluoroorotic acid (5-FOA) resistance. We identified a novel class ofura6mutants that can grow in the presence of 5-FOA. Unlikeura3mutants,ura6mutants remain prototrophic and grow in the absence of uracil. In addition to 5-FOA resistance, we found that mutations toURA6also confer resistance to 5-fluorocytosine (5-FC) and 5-fluorouracil (5-FU). In total, we identified 50 unique missense mutations across 32 residues ofURA6. We found that 28 out of the 32 affected residues are located in regions conserved betweenSaccharomyces cerevisiaeand three clinically relevant pathogenic fungi. These findings suggest that mutations toURA6present a second target for mutation screens utilizing 5-FOA as a selection marker as well as a potential mode of resistance to the antifungal therapeutic 5-FC.