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(Received for publication, March 4, 1996, and in revised form, April 3, 1996)
From the 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 cadmium factor (Ycf1). A chromosomal deletion of
YRS1 lead to viable
Volume 271, Number 25,
Issue of June 21, 1996
pp. 14712-14716
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
,
Department of Fermentation Technology,
Faculty of Engineering, Hiroshima University, Higashi-Hiroshima 739, Japan and the § Institute of Physical and Chemical Research
(Riken), Wako, Saitama 351-01, Japan
yrs1 cells, which
exhibited hypersensitivity to reveromycin A. Elevation of the
YRS1 gene dosage in wild type cells conferred increased
resistance to reveromycin A. By analyzing the effect of
YRS1 disruption and overexpression it was demonstrated that
Yrs1 is involved in the detoxification of a wide range of the organic
anions that contain carboxyl group(s) but none of the other type of
toxic compounds examined. Fluorescence-activated cell sorter analysis
indicated the increased accumulation of the anionic fluorescent
compound rhodamine B in yrs1 cells. The expression of
YRS1 was induced strikingly by reveromycin A. These results
suggest that Yrs1 is a multispecific organic anion transporter
important for tolerance against toxic environmental organic anions.
Yrs1 had an overlapping specificity with Ycf1 in the resistance to
cadmium.
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