Robert F. Brooks

Cell size, cell cycle and transition probability in mouse fibroblasts.

Abstract This paper describes the relationship between cell size and cell division in two situations. In the first, quiescent cells were sorted on the basis of cell size using a fluorescence-activated cell sorter and returned to culture. The results of this type of experiment are compatible with the idea that once cells have completed a size-dependent lag, the rate of entry of cells into S phase is controlled by a rate-limiting random event (or transition). The second kind of experiment follows the kinetics of complete cell cycles in rapidly proliferating cells whose mothers had been sorted on the basis of cell size. The cells born of small mother cells have longer cycle times than cells derived from large mothers. The difference in the cycle time of these two classes was due to differences in the B phase of the cell cycle [containing S, G2, M and part of G1 (G1B)], transition probability being the same in both size classes. Our results show that S, G2 and M are unaffected by size, thus confining the effect of size to G1B. It seems probable that the variability of B phase in cloned cell populations is partly due to variations of cell size at division, and correlations between the cycle times of sister cells result because sibling cells are more similar in size than unrelated cells. The major factor controlling cell division in mouse fibroblasts is shown, however, to be the transition probability; size has a more minor role.

The Transition Probability Model: Successes, Limitations and Deficiencies

The now familiar picture of the eukaryotic cell cycle followed from the discovery that DNA replication usually precedes the visible events of mitosis and cell-division by many hours [1]. For many eukaryotes, mitosis and cell-division are followed by a gap of several hours (G1) before DNA synthesis (S phase) begins, and on completion of DNA replication there is usually another gap (G2) before the cell divides once again.