DNA/Cell Mass Homeostasis: Coordinating DNA Replication and Cell Size with Central Carbon Metabolism During Bacterial...

DNA/cell mass homeostasis is a pervasive feature of living organisms. As the cell grows in response to nutrient availability, it must duplicate each chromosome once and only once each division cycle. Across the eukaryote Tree of Life, cells differ in their sizes in a manner that depends directly on the amount of DNA they harbor, what has been termed the "nucleotypic effect": cell size expands or contracts as DNA content increases or decreases. In eukaryotes, any deviation from DNA/mass homeostasis results in the deregulation of the developmental program and the initiation of carcinogenesis and other genetic pathologies. In bacteria, deviation from, or perturbation of, DNA/mass homeostasis alters important physiological features such as the cell cycle timing of DNA replication initiation and the coordination of initiation with replication termination and cell division. In prokaryotes, the timing of initiation occurs at a relatively constant and growth-rate-invariant mass, termed the initiation mass (Mi), and depends strictly on DNA replication fork rates and membrane biogenesis. Complex "machines", frequently referred to as hyperstructures or factories, mediate the phase transitions that define the different periods of the bacterial cell cycle. The following will examine how DNA/mass homeostasis maintains a balance between DNA replication initiation and elongation in order to gate the phase transitions that organize the cell cycle in time and space.