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

Vishwanatha, Akshay and Rallis, Charalampos and Bevkal Subramanyaswamy, Shubha and D'Souza, Cletus Joseph Michael and Bähler, Jürg and Schweingruber, Martin Ernst (2016) 'Identification of nuclear genes affecting 2-Deoxyglucose resistance in Schizosaccharomyces pombe.' FEMS Yeast Research, 16 (6). fow061-fow061. ISSN 1567-1356

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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.

Item Type: Article
Uncontrolled Keywords: Schizosaccharomyces; Deoxyglucose; Antimetabolites; Drug Resistance, Fungal; Gene Expression; Gene Deletion; Genes, Fungal; Genetic Testing
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 18 Jun 2021 14:49
Last Modified: 18 Aug 2022 10:32

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