Identification of nuclear genes affecting 2-Deoxyglucose resistance in Schizosaccharomyces pombe

2-Deoxyglucose (2-DG) is a toxic glucose analog. To identify genes involved in 2-DG toxicity in Schizosaccharomyces pombe, we
screened a wild-type overexpression library for genes which render cells 2-DG resistant. A gene we termed odr1, encoding
an uncharacterized hydrolase, led to strong resistance and altered invertase expression when overexpressed. We speculate
that Odr1 neutralizes the toxic form of 2-DG, similar to the Saccharomyces cerevisiae Dog1 and Dog2 phosphatases which
dephosphorylate 2-DG-6-phosphate synthesized by hexokinase. In a complementary approach, we screened a haploid
deletion library to identify 2-DG-resistant mutants. This screen identified the genes snf5, ypa1, pas1 and pho7. In liquid
medium, deletions of these genes conferred 2-DG resistance preferentially under glucose-repressed conditions. The
deletion mutants expressed invertase activity more constitutively than the control strain, indicating defects in the control
of glucose repression. No S. cerevisiae orthologs of the pho7 gene is known, and no 2-DG resistance has been reported for any
of the deletion mutants of the other genes identified here. Moreover, 2-DG leads to derepressed invertase activity in S.
pombe, while in S. cerevisiae it becomes repressed. Taken together, these findings suggest that mechanisms involved in 2-DG
resistance differ between budding and fission yeasts.