title: Genetic evidence for a link between glycolysis and DNA replication.
abstract: BACKGROUND
  A challenging goal in biology is to understand how the principal cellular functions are integrated so that cells achieve viability and optimal fitness in a wide range of nutritional conditions.
  
  
  RESULTS
  We report here a tight link between glycolysis and DNA synthesis. The link, discovered during an analysis of suppressors of thermosensitive replication mutants in bacterium Bacillus subtilis, is very strong as some metabolic alterations fully restore viability to replication mutants in which a lethal arrest of DNA synthesis otherwise occurs at a high, restrictive, temperature. Full restoration of viability by such alterations was limited to cells with mutations in three elongation factors (the lagging strand DnaE polymerase, the primase and the helicase) out of a large set of thermosensitive mutants affected in most of the replication proteins. Restoration of viability resulted, at least in part, from maintenance of replication protein activity at high temperature. Physiological studies suggested that this restoration depended on the activity of the three-carbon part of the glycolysis/gluconeogenesis pathway and occurred in both glycolytic and gluconeogenic regimens. Restoration took place abruptly over a narrow range of expression of genes in the three-carbon part of glycolysis. However, the absolute value of this range varied greatly with the allele in question. Finally, restoration of cell viability did not appear to be the result of a decrease in growth rate or an induction of major stress responses.
  
  
  CONCLUSIONS
  Our findings provide the first evidence for a genetic system that connects DNA chain elongation to glycolysis. Its role may be to modulate some aspect of DNA synthesis in response to the energy provided by the environment and the underlying mechanism is discussed. It is proposed that related systems are ubiquitous.
authors.affiliation: Laboratoire de Génétique Microbienne, INRA, Jouy en Josas, France. laurent.janniere@jouy.inra.fr
authors.forename: Laurent
authors.initials: L
authors.lastname: Jannière
authors.forename: Danielle
authors.initials: D
authors.lastname: Canceill
authors.forename: Catherine
authors.initials: C
authors.lastname: Suski
authors.forename: Sophie
authors.initials: S
authors.lastname: Kanga
authors.forename: Bérengère
authors.initials: B
authors.lastname: Dalmais
authors.forename: Roxane
authors.initials: R
authors.lastname: Lestini
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Monnier
authors.forename: Jérôme
authors.initials: J
authors.lastname: Chapuis
authors.forename: Alexander
authors.initials: A
authors.lastname: Bolotin
authors.forename: Marina
authors.initials: M
authors.lastname: Titok
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Le Chatelier
authors.forename: S Dusko
authors.initials: SD
authors.lastname: Ehrlich
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D005798:Genes, Bacterial; D006019:Glycolysis; D009154:Mutation