Ubiquitin-conjugating enzymes involved in sensitivity to methylmercury in yeast were identified by deletion analysis, which showed that Ubc2- or Ubp13-deficiency conferred resistance to methylmercury. Whi2, which was previously shown to be associated with increased methylmercury toxicity and is intracellularly degraded via the ubiquitin-proteasome system, was expressed at significantly lower levels in Ubc2-deficient yeast than in wild-type yeast. Ubc2/Whi2 double-deficient yeast showed neither an additive nor synergistic increase in methylmercury resistance. Our results indicate that Ubc2 may increase the sensitivity to methylmercury in yeast by inhibiting the proteasomal degradation of Whi2.