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Intégrative biology: discovered of a bond between nutrition and synthesis of the ADN
:: 17 May, 2007
For a few years, the biologists have sought to acquire a total sight of the alive world while trying to include/understand how the activity of the great cellular functions is adjusted in order to allow survival and an optimal growth of the cells, even under extreme nutritional conditions.
The researchers of the INRA and CNRS have just shown by genetic methods that, in the bacterium models Bacillus subtilis, the carbonaceous central metabolism (which produces energy starting from food) and the replication (which synthesizes the ADN), two central cellular functions in the fields of the nutrition and heredity, are closely dependent. The detail of work is published on May 16, 2007 in PLoS ONE. The bond highlighted by the researchers implies the activity of a small area of the carbonaceous central metabolism (final reactions of the glycolysis which degrades sugars) and certain enzymes of the machinery ensuring the synthesis of the ADN. This bond would depend on metabolic signals, emitted according to the identified activity of the metabolic area, which would be perceived, directly or indirectly, by the enzymes of replication. This would result in to adjust the speed of the synthesis of the ADN and the stability of the replicative machinery to the richness of the nutritive medium and thus at the speed of growth of the cells.
The enzymes of the carbonaceous central metabolism, essential and strongly preserved in the alive beings, of simplest with most complex, would thus have at the same time a metabolic role and a regulating role. These results, obtained in bacteria, are to be brought closer observations made on the higher organizations, connecting the metabolism of sugars to the transcription, the apoptose (the programmed death of the cells) and the nerve impulse, in order to adjust the activity of great biological functions to the richness of the surrounding medium.
In addition to one major fundamental interest, the bond metabolism/replication could also have a medical impact since early events of carcinogenesis, generally including a deregulation of glycolysis (the Warburg effect) and a reduction in the fidelity of the replication and stability of the ADN, could imply disturbances in the relation metabolism/replication.
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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.
Methodology/Principal Findings
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/Significance
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.
References: Genetic Evidence for has Link Between Glycolysis and DNA Replication Laurent Jannière, Danielle Canceill, Catherine Suski, Sophie Kanga, Berengere Dalmais, Roxane Lestini, Anne-Francoise Monnier, Jerome Chapuis, Alexander Bolotin, Marina Titok, Emmanuelle Chatelier and S. Dusko Ehrlich.
Contacts: Laurent JANNIERE Unit of Microbial “Genetic” research, department “Microbiology and food chain”, center INRA of Jouy-in-Josas
Tel.: 01 34 65 25 09 laurent.janniere@jouy.inra.fr
Contact presses: Service of press INRA, Tel.: 01 42 75 91 69 Service of press CNRS, Tel.: 01 44 96 51 51
