title: A haploproficient interaction of the transaldolase paralogue NQM1 with the transcription factor VHR1 affects stationary phase survival and oxidative stress resistance.
abstract: BACKGROUND
  Studying the survival of yeast in stationary phase, known as chronological lifespan, led to the identification of molecular ageing factors conserved from yeast to higher organisms. To identify functional interactions among yeast chronological ageing genes, we conducted a haploproficiency screen on the basis of previously identified long-living mutants. For this, we created a library of heterozygous Saccharomyces cerevisiae double deletion strains and aged them in a competitive manner.
  
  
  RESULTS
  Stationary phase survival was prolonged in a double heterozygous mutant of the metabolic enzyme non-quiescent mutant 1 (NQM1), a paralogue to the pentose phosphate pathway enzyme transaldolase (TAL1), and the transcription factor vitamin H response transcription factor 1 (VHR1). We find that cells deleted for the two genes possess increased clonogenicity at late stages of stationary phase survival, but find no indication that the mutations delay initial mortality upon reaching stationary phase, canonically defined as an extension of chronological lifespan. We show that both genes influence the concentration of metabolites of glycolysis and the pentose phosphate pathway, central metabolic players in the ageing process, and affect osmolality of growth media in stationary phase cultures. Moreover, NQM1 is glucose repressed and induced in a VHR1 dependent manner upon caloric restriction, on non-fermentable carbon sources, as well as under osmotic and oxidative stress. Finally, deletion of NQM1 is shown to confer resistance to oxidizing substances.
  
  
  CONCLUSIONS
  The transaldolase paralogue NQM1 and the transcription factor VHR1 interact haploproficiently and affect yeast stationary phase survival. The glucose repressed NQM1 gene is induced under various stress conditions, affects stress resistance and this process is dependent on VHR1. While NQM1 appears not to function in the pentose phosphate pathway, the interplay of NQM1 with VHR1 influences the yeast metabolic homeostasis and stress tolerance during stationary phase, processes associated with yeast ageing.
authors.affiliation: Max Planck Institute for Molecular Genetics, Ihnestr 73, Berlin, 14195, Germany. michel@molgen.mpg.de.
authors.forename: Steve
authors.initials: S
authors.lastname: Michel
authors.affiliation: Department of Biochemistry and Cambridge Systems Biology Center, University of Cambridge, 80, Tennis, Court Road, Cambridge, CB2 1GA, UK. mk747@cam.ac.uk.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Keller
authors.affiliation: Metabolic Unit, Department of Clinical Chemistry, VU University Medical Centre Amsterdam, Amsterdam, The Netherlands. m.wamelink@vumc.nl.
authors.forename: Mirjam M C
authors.initials: MM
authors.lastname: Wamelink
authors.affiliation: Department of Biochemistry and Cambridge Systems Biology Center, University of Cambridge, 80, Tennis, Court Road, Cambridge, CB2 1GA, UK. mr559@cam.ac.uk.|MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK. mr559@cam.ac.uk.
authors.forename: Markus
authors.initials: M
authors.lastname: Ralser
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006019:Glycolysis; D009995:Osmosis; D018384:Oxidative Stress; D010427:Pentose Phosphate Pathway; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014153:Transaldolase / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C511614:Vhr1 protein, S cerevisiae; D014153:Transaldolase; C587993:TAL1 protein, S cerevisiae