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).
