Abstract
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key metabolic regulator implicated in a variety of cellular processes. It functions as a glycolytic enzyme, a protein kinase, and a metabolic switch under oxidative stress. Its enzymatic inactivation causes a major shift in the primary carbohydrate flux. Furthermore, the protein is implicated in regulating transcription, ER-to-Golgi transport, and apoptosis. We found that Saccharomyces cerevisiae cells null for all GAPDH paralogues (Tdh1, Tdh2, and Tdh3) survived the counter-selection of a GAPDH-encoding plasmid when the NAD(+) metabolizing deacetylase Sir2 was overexpressed. This phenotype required a fully functional copy of SIR2 and resulted from hyper-recombination between S. cerevisiae plasmids. In the wild-type background, GAPDH overexpression increased the plasmid recombination rate in a growth-condition dependent manner. We conclude that GAPDH influences yeast episome stability via Sir2 and propose a model for the interplay of Sir2, GAPDH, and the glycolytic flux.
MeSH terms
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Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / genetics
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Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / metabolism
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Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
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Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
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Glycolysis / genetics*
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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Plasmids / genetics*
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Plasmids / metabolism
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Recombination, Genetic*
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Saccharomyces cerevisiae / enzymology*
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / physiology
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Silent Information Regulator Proteins, Saccharomyces cerevisiae / genetics
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Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism*
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Sirtuin 2
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Sirtuins / genetics
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Sirtuins / metabolism*
Substances
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Saccharomyces cerevisiae Proteins
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Silent Information Regulator Proteins, Saccharomyces cerevisiae
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Glyceraldehyde-3-Phosphate Dehydrogenases
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Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
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TDH1 protein, S cerevisiae
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TDH2 protein, S cerevisiae
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TDH3 protein, S cerevisiae
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SIR2 protein, S cerevisiae
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Sirtuin 2
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Sirtuins
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Histone Deacetylases