Cell populations go through a particular type of exponential growth called doubling. Thus, each generation of cells should be twice as numerous as the previous generation. However, the number of generations only gives a maximum figure as not all cells survive in each generation.
Cell size is highly variable among organisms, with some algae such as Caulerpa taxifolia being a single cell several meters in length. Plant cells are much larger than animal cells, and protists such as Paramecium can be 330 μm long, while a typical human cell might be 10 μm. How these cells "decide" how big they should be before dividing is an open question. Chemical gradients are known to be partly responsible, and it is hypothesized that mechanical stress detection by cytoskeletal structures is involved. Work on the topic generally requires an organism whose cell cycle is well-characterized.
The relationship between cell size and cell division has been extensively studied in yeast. For some cells, there is a mechanism by which cell division is not initiated until a cell has reached a certain size. If the nutrient supply is restricted (after time t = 2 in the diagram, below), and the rate of increase in cell size is slowed, the time period between cell divisions is increased. Yeast cell-size mutants were isolated that begin cell division before reaching a normal/regular size (wee mutants).
Wee1 protein is a tyrosine kinase that normally phosphorylates the Cdc2 cell cycle regulatory protein (the homolog of CDK1 in humans), a cyclin-dependent kinase, on a tyrosine residue. Cdc2 drives entry into mitosis by phosphorylating a wide range of targets. This covalent modification of the molecular structure of Cdc2 inhibits the enzymatic activity of Cdc2 and prevents cell division. Wee1 acts to keep Cdc2 inactive during early G2 when cells are still small. When cells have reached sufficient size during G2, the phosphatase Cdc25 removes the inhibitory phosphorylation, and thus activates Cdc2 to allow mitotic entry. A balance of Wee1 and Cdc25 activity with changes in cell size is coordinated by the mitotic entry control system. It has been shown in Wee1 mutants, cells with weakened Wee1 activity, that Cdc2 becomes active when the cell is smaller. Thus, mitosis occurs before the yeast reach their normal size. This suggests that cell division may be regulated in part by dilution of Wee1 protein in cells as they grow larger.
The protein kinase Cdr2 (which negatively regulates Wee1) and the Cdr2-related kinase Cdr1 (which directly phosphorylates and inhibits Wee1 in vitro) are localized to a band of cortical nodes in the middle of interphase cells. After entry into mitosis, cytokinesis factors such as myosin II are recruited to similar nodes; these nodes eventually condense to form the cytokinetic ring. A previously uncharacterized protein, Blt1, was found to colocalize with Cdr2 in the medial interphase nodes. Blt1 knockout cells had increased length at division, which is consistent with a delay in mitotic entry. This finding connects a physical location, a band of cortical nodes, with factors that have been shown to directly regulate mitotic entry, namely Cdr1, Cdr2, and Blt1.
Further experimentation with GFP-tagged proteins and mutant proteins indicates that the medial cortical nodes are formed by the ordered, Cdr2-dependent assembly of multiple interacting proteins during interphase. Cdr2 is at the top of this hierarchy and works upstream of Cdr1 and Blt1. Mitosis is promoted by the negative regulation of Wee1 by Cdr2. It has also been shown that Cdr2 recruits Wee1 to the medial cortical node. The mechanism of this recruitment has yet to be discovered. A Cdr2 kinase mutant, which is able to localize properly despite a loss of function in phosphorylation, disrupts the recruitment of Wee1 to the medial cortex and delays entry into mitosis. Thus, Wee1 localizes with its inhibitory network, which demonstrates that mitosis is controlled through Cdr2-dependent negative regulation of Wee1 at the medial cortical nodes.
Cell polarity factors positioned at the cell tips provide spatial cues to limit Cdr2 distribution to the cell middle. In fission yeast Schizosaccharomyces pombe (S. Pombe), cells divide at a defined, reproducible size during mitosis because of the regulated activity of Cdk1. The cell polarity protein kinase Pom1, a member of the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) family of kinases, localizes to cell ends. In Pom1 knockout cells, Cdr2 was no longer restricted to the cell middle, but was seen diffusely through half of the cell. From this data it becomes apparent that Pom1 provides inhibitory signals that confine Cdr2 to the middle of the cell. It has been further shown that Pom1-dependent signals lead to the phosphorylation of Cdr2. Pom1 knockout cells were also shown to divide at a smaller size than wild-type, which indicates a premature entry into mitosis.