HOL1 mutations confer novel ion transport in Saccharomyces cerevisiae

Saccharomyces cerevisiae histidine auxotrophs are unable to use L-histidinol as a source of histidine even when they have a functional histidinol dehydrogenase. Mutations in the hol1 gene permit growth of His^- cells on histidinol by enhancing the ability of cells to take up histidinol from the medium. Second-site mutations linked to HOL1-1 further increase histidinol uptake. HOL1 double mutants and, to a lesser extent, HOL1-1 single mutants show hypersensitivity to specific cations added to the growth medium, including Na⁺, Li⁺, Cs⁺, Be²⁺, guanidinium ion, and histidinol, but not K⁺, Rb⁺, Ca²⁺, or Mg²⁺. The Na⁺-hypersensitive phenotype is correlated with increased uptake and accumulation of this ion. The HOL1-1-101 gene was cloned and used to generate a viable haploid strain containing a hol1 deletion mutation (hol1Δ). The uptake of cations, the dominance of the mutant alleles, and the relative inability of hol1Δ cells to take up histidinol or Na⁺ suggest that hol1 encodes an ion transporter. The novel pattern of ion transport conferred by HOL1-1 and HOL1-1-101 mutants may be explained by reduced selectivity for the permeant ions.