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Linked : DNA Synthesis and Carbon Metabolism

A close link between DNA replication and carbon metabolism, which produces energy and building blocks from nutrients, has been established by scientists from CNRS and INRA,1 a discovery which makes one chapter of what biochemistry textbooks have hitherto identified as two separate biological processes.

Laurent Jannière's team2 studied suppressors of thermosensitive replication mutants in the bacterium Bacillus subtilis.3 They found that replication mutants, otherwise rendered incapable of further DNA synthesis by high, restrictive temperature, were restored to viability by mutations in metabolic genes. The phenomenon of mutation suppression in genetics is evidence of a functional link between proteins. At a molecular level, it suggests that the structural defect due to the mutation in the first protein can be alleviated by a mutation in the “suppressive” one. In this case, the suppressive genes belong to one key part of carbon metabolism called glycolysis, in which glucose is broken down by enzymes into pyruvic acid.

Jannière and his colleagues suggest metabolic signals generated according to the activity of the terminal stage of glycolysis are sensed by replication enzymes to produce a functional change in the replication machinery. This restores replication and growth activity in the damaged mutants at restrictive temperatures.

This is the first evidence for a genetic system that connects DNA chain elongation to glycolysis. Its role may be to adapt DNA synthesis and therefore cell multiplication to the energy available in the environment at a given time. The discovery suggests that carbon metabolism regulates key cellular functions and helps explain the essential role of certain of its enzymes.

The revelation of a strong, likely ancestral and universal genetic program connecting metabolism with replication is of utmost interest to understand how cells adapt to their environment. But it could also be important for medical research, since early events in carcinogenesis generally include increased glycolysis and a decrease in DNA stability and replication fidelity–disorders that may involve this newly uncovered link between replication and metabolism.


Graham Tearse

Notes :

1. Institut national de la recherche agronomique.
2. Unité de génétique microbienne (CNRS/ INRA).
3. PloS ONE. 2(5): e447. 2007.

Contacts :

Laurent Jannière,
INRA, Jouy-en-Josas.


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