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GFAT as a target molecule of methylmercury toxicity in Saccharomyces cerevisiae

Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan; and
^* Department of Microbiology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan

¹Correspondence: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan. E-mail: naganuma{at}mail.pharm.tohoku.ac.jp

Using a genomic library constructed from Saccharomyces cerevisiae, we have identified a gene GFA1 that confers resistance to methylmercury toxicity. GFA1 encodes L-glutamine:D-fructose-6-phosphate amidotransferase (GFAT) and catalyzes synthesis of glucosamine-6-phosphate. Transformed yeast cells expressing GFA1 demonstrated resistance to methylmercury but no resistance to p-chloromercuribenzoate, a GFAT inhibitor. The cytotoxicity of methylmercury was inhibited by loading excess glucosamine 6-phosphate into yeast. Considering that GFAT is an essential cellular enzyme, our findings suggest that GFAT is the major target molecule of methylmercury in yeasts. This report is the first to identify the target molecule of methylmercury toxicity in eukaryotic cells.—Naganuma, A., Miura, N., Kaneko, S., Mishina, T., Hosoya, S., Miyairi, S., Furuchi, T., Kuge, S. GFAT as a target molecule of methylmercury toxicity in Saccharomyces cerevisiae.

Key Words: gene screening • glucosamine • glucosamine-6-phosphate • resistance • p-chloromercuribenzoate

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