Does the Initiation of Chromosome Replication Regulate Cell Division?

Abstract

The chapter discusses whether size of cells engaged in initiation of DNA replication has smaller variance than the size of cells in the act of cytoplasmic division, and whether the time intervals among various stages of the cell cycle are distributed with large or small variance for cells within a balanced growing population. The simulations exclude models in which initiation of replication takes place only when a cell has grown and reached a precise size, the auto- radiographic data can only be fitted on the assumption that there is at least 15% coefficient of variation in the size of cells at initiation. Although the computer modeling shows that there is considerable variation in cell size at initiation, it is less sure whether there is a comparable, or greater, variation in cell size at initiation than there is at division. If the variation is greater at initiation, then this less precise process cannot control nor time the more precise process of cell division. Together these considerations argue against the class of hypotheses in which cell division is timed relative to some aspect of chromosomal synthesis, and for a variation on the model in which both chromosome initiation and cell division are independently triggered by some aspects of cell growth. The analysis results are fully consistent with a single trigger controlling initiation, which deterministically and precisely controls the rest of the cell cycle, except for some additional variability in the actual size of separation of divided cells.