Coupling the cell cycle to cell growth

Abstract

In order to multiply, both prokaryotic and eukaryotic cells go through a series of events that are collectively called the cell cycle. However, DNA replication, mitosis and cell division may also be viewed as having their own, in principle independent, cycles, which are tied together by mechanisms extrinsic to the cell cycle--the checkpoints--that maintain the order of events. We propose that our understanding of cell-cycle regulation is enhanced by viewing each event individually, as an independently regulated process. The nature of the parameters that regulate cell-cycle events is discussed and, in particular, we argue that cell mass is not such a parameter.

Figure 1

Examples of independence of cell-cycle events. (A) S phase can be independent of cytokinesis. Escherichia coli cells were grown exponentially in rich medium (left) or treated with ampicillin (right) for 90 min, fixed in ethanol and stained with DAPI (blue) for visualization of nucleoids. The images were obtained by phase-contrast and fluorescence microscopy. (B) Mitosis can occur independently of S phase. Schizosaccharomyces pombe cdc10^ts rad3 mutant cells were incubated for 6 h at the non-restrictive temperature for cdc10^ts, a treatment that arrests the cells before S phase. Four different cells are shown. In the absence of the checkpoint protein Rad3 (the founding member of the ATR family of proteins), the cells proceed to mitosis and attempt to divide a single nucleus. The DNA is stained by DAPI (light foci located at the septum). Note the unequal amounts of DNA distributed to the two daughter cells. ATR, ataxia-tengiectasia mutated and Rad3-related; cdc10^ts, cell division cycle 10 temperature-sensitive mutant.

Figure 2

Representation of the cell cycle as being composed of three linear and repetitive series of S phase (S), mitosis (M) and cytokinesis (C). (A) In this simplified model, the three series of events would be regulated individually and coupled to cell growth in an unknown manner. (B) In reality, they are coupled to one another more directly through checkpoint mechanisms. Cues are given to inhibit another process (blocked arrows) or allow it to continue (arrows).

Figure 3

Two-parametric histogram of a cell culture growing under steady-state conditions. The cell cycle is composed of a G1 phase (G1), S phase (S), G2 phase (G2), mitosis (M) and cytokinesis (C).