What is it about?
DNA replication is under the control of metabolism and little is known about the underlying mechanism. We show here that an enzyme of the central carbon metabolism is important for the initiation and elongation phase of replication. This commitment depends on amino acids of the metabolic enzyme which bind its substrates, are involved in signalling, and on direct interactions with replication enzymes. It is in contrast independent on the metabolic activity of the enzyme.
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Why is it important?
Our results show that the metabolic enzyme has a previously unknown non-metabolic function which connects replication to key metabolites of central carbon metabolism. We propose that this enzyme is a prototype for a new family of replication regulators that operate in the metabolic control of replication to assist replication gating in a wide range of growth conditions.
Perspectives
This work lays the foundations for wider studies on the role played by central carbon metabolism in the metabolic control of replication and opens new perspectives on events linking two early and fundamental changes that pave the way to carcinogenesis: the Warburg effect and the genetic instability.
Dr Laurent Janniere
Genopole, CNRS, UEVE, Paris-Saclay
Read the Original
This page is a summary of: Glycolytic pyruvate kinase moonlighting activities in DNA replication initiation and elongation, July 2020, Cold Spring Harbor Laboratory Press,
DOI: 10.1101/2020.07.07.191163.
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