The Cell Cycle
The cell division cycle, generally known simply as the cell cycle, is a complex process that lies at the heart of haemopoiesis. Dysregulation of cell proliferation is also the key to the development of malignant disease. The duration of the cell cycle is variable between different tissues but the basic principles remain constant. The cycle is divided into the mitotic phase (M phase), during which the cell physically divides, and interphase, during which the chromosomes are duplicated and cell growth occurs prior to division (Fig. 1.7). The M phase is further partitioned into classical mitosis, in which nuclear division is accomplished, and cytokinesis, in which cell fission occurs.
Interphase is divided into three main stages: a G1 phase, in which the cell begins to commit to replication, an S phase, during which DNA content doubles and the chromosomes replicate, and the G2 phase, in which the cell organelles are copied and cytoplasmic volume is increased. If cells rest prior to division they enter a G0 state where they can remain for long periods of time. The number of cells at each stage of the cell cycle can be assessed by exposing cells to a chemical or radiolabel that gets incorporated into newly generated DNA or by flow cytometry.
The cell cycle is controlled by two checkpoints which act as brakes to coordinate the division process at the end of the G1 and G2 phases. Two major classes of molecules control these checkpoints, cyclin‐dependent protein kinases (Cdk), which phosophorylate downstream protein targets, and cyclins, which bind to Cdks and regulate their activity. An example of the importance of these systems is demonstrated by mantle cell lymphoma which results from the constitutive activation of cyclin D1 as a result of a chromosomal translocation (see p. 223).