Enzymes of the central carbon metabolism: Are they linkers between transcription, DNA replication, and carcinogenesis?

Abstract

Dependence of carcinogenesis on disruption of DNA replication regulation is a well-known fact. There are also many reports demonstrating the interplay between transcription and DNA replication processes, particularly underlying the importance of promoter activities in the control of replication initiation. Recent findings have shown direct links between central carbon metabolism and DNA replication regulation. Here, we summarize previously published reports which indicated that enzymes of the central carbon metabolism, particularly those involved in glycolysis and the tricarboxylic acid cycle, may contribute to regulation of transcription and DNA transactions (replication and repair). In this light, we propose a hypothesis that some of these enzymes might be linkers between transcription, DNA replication, and carcinogenesis. If true, it may have a consequence in our understanding of causes and mechanisms of carcinogenesis. Particularly, certain metabolic perturbations might directly (through central carbon metabolism enzymes) influence regulation of DNA transactions (replication control and fidelity), and thus facilitate carcinogenesis. To test this hypothesis, further studies will be necessary, which is discussed in the final part of this article.