Methylmercury is a known pollutant that causes severe central nervous system disorders. It is capable of passing through the blood-brain barrier and accumulates in cerebral cells. However, little is known regarding the mechanism of its toxicity at the molecular level. Using yeast cells, we searched for the genes involved in the expression of methylmercury toxicity, and found that genes encoding L-glutamine • D-fructose-6-phosphate amidotransferase (GFAT) and ubiquitin transferase (Ubc3) confer methylmercury resistance on the cells. It has also been shown that GFAT is the target molecule of methylmercury in yeast cells. These findings provide important clues about the mechanism underlying methylmercury toxicity in mammals. © 2002 Tohoku University Medical Press.