Cell cycle progression: computer simulation of uncoupled subcycles of DNA replication and cell growth.

A computer simulation is presented for cell proliferation in a structured cell cycle model. The simulation takes into account the idea that DNA replication and cell growth are two loosely coupled subcycles. The simulation experiments performed offer an explanation for the close correlation often found in interdivision times of sister cell pairs and demonstrate that the exponential slope of the so-called beta-curve is linked to an exponential increase in cell mass. However, in synchronization experiments, a linear increase in mean mass of a cell population develops over time. A channel is opened for a genetic and growth rate influence extending from grandparent to granddaughter. Positive and negative time correlations close to zero still occurred for mother-daughter cell cycles. The computer program leaves two sites in the cell cycle available for gene, molecular and size checkpoints, one in G1 and one in G2. The simulation experiments bridge the gap between models considering (i) size control, (ii) transition probability, and (iii) inherited properties as interpretations of cell cycle progression and are applicable to embryonic cells with the potential to differentiate, somatic cells, and to the kinetics of activation of serum-starved cells. A G0 state is also defined.