We found that overexpression of Bop3, a protein of unknown function, confers resistance to methylmercury in Saccharomyces cerevisiae. Bmh2, Fkh1, and Rts1 are proteins that have been previously shown to bind Bop3 by the two-hybrid method. Overexpression of Bmh2 and the homologous protein Bmh1 confers resistance to methylmercury in yeast, but overexpression of either Fkh1 or Rts1 has a minimal effect. However, the increased level of resistance to methylmercury produced by overexpression of Bop3 was smaller in Fhk1-deleted yeast as compared with that of the wild-type strain. In contrast, the degree of resistance was significantly elevated in Rts1-deleted yeast. Msn2 and Msn4 were previously reported as proteins that bind to Bmh1 and Bmh2. Overexpression of Msn2 conferred a much greater sensitivity to methylmercury in yeast, while deletion of the corresponding gene lowered the degree of resistance to methylmercury induced by overexpression of Bop3. These results suggest that multiple proteins are involved in minimizing the toxicity of methylmercury induced by overexpression of Bop3. (c) 2005 Elsevier Inc. All rights reserved.