THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) SUBFAMILY (YRS1 YOR1) OF SACCHAROMYCES-CEREVISIAE IS IMPORTANT FOR THE TOLERANCE TO A BROAD RANGE OF ORGANIC-ANIONS/

We have cloned and characterized a Saccharomyces cerevisiae gene YRS1 that complements the phenotype of the mutant sensitive to the anionic drug reveromycin A, The YRS1 gene, which is identical to the recently identified YOR1 gene, encodes a protein with extensive homology to the human multidrug resistance-associated protein (MRP) and the yeast cad mium factor (Ycf1), A chromosomal deletion of YRS1 lead to viable Delt a yrs1 cells, which exhibited hypersensitivity to reveromycin A. Eleva tion of the YRS1 gene dosage in wild type cells conferred increased re sistance to reveromycin A, By analyzing the effect of YRS1 disruption and overexpression it was demonstrated that Yrs1 is involved in the de toxification of a wide range of the organic anions that con tain carbo xyl group(s) but none of the other type of toxic compounds examined, F luorescence-activated cell sorter analysis indicated the increased acc umulation of the anionic fluorescent compound rhodamine B in Delta yrs 1 cells, The expression of YRS1 was induced strikingly by reveromycin A. These results suggest that Yrs1 is a multispecific organic anion tr ansporter important for tolerance against toxic environmental organic anions, Yrs1 had an overlapping specificity with Ycf1 in the resistanc e to cadmium.