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Cell Cycle and Cell Division
Editor(s): Zhaohua Tang, Ivor Hickey |
The study of the cell cycle focuses on mechanisms that regulate the timing and frequency
of DNA duplication and cell division. As a biological concept, the cell cycle is defined as
the period between successive divisions of a cell. During this period, the contents of the
cell must be accurately replicated. Microscopists had known about cell division for more
than one hundred years, but not until the 1950s, through the pioneering work of Alma
Howard and Stephen Pelc, did they become aware that DNA replication took place only
at a specific phase of the cell cycle and that this phase was clearly separated from mitosis.
Howard and Pelc's work in the broad bean, Vicia faba, revealed that the cell goes through
many discrete phases before and after cell division. From this understanding, scientists
then identified the four characteristic phases of the cell cycle: mitosis (M), gap 1 (G1),
DNA synthesis (S), and gap 2 (G2). The study of these phases, the proteins that regulate
them, and the complex biochemical interactions that stop or start DNA replication and
cell division (cytokinesis) are the primary concerns of cell cycle biologists.
The most significant progress in this research field came with the demonstration that
specific protein complexes involving cyclins were critical for regulating the passage of
cells through the cell cycle. These early observations came from biological studies of the
cells of rapidly dividing fertilized frog eggs as well as mutant yeast cells that could not
divide. The observations suggested that regulation of the cell cycle is conserved
throughout eukaryotes, which has since proved to be the case. The mechanism of division
in bacteria differs from that of eukaryotes, and the control of their cell cycle is also
somewhat different, although again it is linked with DNA replication.
Although the cell cycle is a highly integrated process, distinct areas of interest within this
field of study have emerged. For instance, many genes and proteins that influence the
passage from one phase of the cell cycle to another have been identified. When their
expression is altered by mutation or aberrant regulation, they are usually classed as
oncogenes. Other proteins act to hold the cell at distinct points in the cycle (checkpoints)
and are known as tumor suppressor genes. Apart from those with a clearly regulatory
role, many proteins have important functions in other aspects of the cell cycle; one is
replication of DNA and organelles, which is a fascinating process that includes its own
repair mechanisms and self-editing. Other fields focus primarily on the mechanical
processes of cell cleavage into two daughter cells at the end of mitosis and on the
condensation and decondensation of chromatin.
How does the cell cycle affect our daily lives? Indeed, most cancers are the result of
inappropriate cell division, often stemming from aberrations in normal cell cycle
regulation. Considerable research is directed to identifying alterations in cell cycle
regulatory proteins, both as targets for therapeutic intervention and as biomarkers that
may indicate prognoses for tumors. In addition, the field of stem cell biology is closely
linked to cell cycle regulation because these pluripotent cells can divide slowly over long
periods and yet initiate growth and differentiation when required. Other areas of current
research include investigating cell cycle regulation in the growth of organs and in
regeneration, where dormant cells can be switched back into a replicative state.
How have scientists studied the cell cycle? Originally, cell cycle studies were the
preserve of microscopy, but today many specific techniques in addition to those widely
employed in cell and molecular biology are applied. Fluorescence-activated cell sorting
has allowed biologists to both identify cells at particular points of the cell cycle and
isolate them. It is possible to monitor how cells that have been exposed to different agents
can progress through the cycle. Central to the identification and isolation of key genes
has been the ability to isolate temperature-sensitive mutant yeast cells that can be blocked
at certain stages of the cycle for closer study. The ability to synchronize cultures so that
all cells are at the same point in the cell cycle has also been a boon to capturing a glimpse
of common mechanisms and isolating key proteins.
Although we now know much about the regulation of the cell cycle, it is clear that we
have a long way to go, particularly in understanding the complexity of the interactions
between the vast multitude of proteins already identified. Current research has identified
a large number of signaling pathways, many comprising several genes, involved in
regulating progression through the cycle. Several of these pathways can interact, and
knowledge of these interactions will be vital to developing effective strategies for
intervention in cancer and other growth abnormalities, such as developmental
deformities. In addition, how the cell cycle responds to DNA damage is an area of active
research because random aberrations in replication and even environmental toxins can
affect vulnerable DNA strands. Ultimately, the success of stem cell-based therapies will
depend on a detailed knowledge of how cells can be maintained through many divisions
without losing their potential to differentiate or transform into tumor precursors. The
study of the cell cycle has vast relevance to the health, well-being, and biology of all
organisms, from the growth and development of these organisms, to cancer and aging
humans, to the potential for disease and injury repair via stem cell therapies.
Image: Steve Gschmeissner/Science Source.