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PLoS One. 2009;4(4):e5376. doi: 10.1371/journal.pone.0005376. Epub 2009 Apr 24.

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

Author information

1
Max Planck Institute for Molecular Genetics, Berlin, Germany. ralser@molgen.mpg.de

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.

PMID:
19390637
PMCID:
PMC2670500
DOI:
10.1371/journal.pone.0005376
[Indexed for MEDLINE]
Free PMC Article

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