Interfering with glycolysis causes Sir2-dependent hyper-recombination of Saccharomyces cerevisiae plasmids.

Max Planck Institute for Molecular Genetics, Berlin, Germany.
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:
Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), Glyceraldehyde-3-Phosphate Dehydrogenases, Glycolysis, Histone Deacetylases, Plasmids, Recombination, Genetic, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 2, Sirtuins
PLoS ONE Apr. 25, 2009; 4(4);e5376 [PUBMED:19390637]
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