Genetic evidence for a link between glycolysis and DNA replication.
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.
Jannière
Laurent
L
Laboratoire de Génétique Microbienne, INRA, Jouy en Josas, France. laurent.janniere@jouy.inra.fr
Canceill
Danielle
D
Suski
Catherine
C
Kanga
Sophie
S
Dalmais
Bérengère
B
Lestini
Roxane
R
Monnier
Anne-Françoise
AF
Chapuis
Jérôme
J
Bolotin
Alexander
A
Titok
Marina
M
Le Chatelier
Emmanuelle
E
Ehrlich
S Dusko
SD
D001412:Bacillus subtilis / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D005798:Genes, Bacterial; D006019:Glycolysis; D009154:Mutation