WEB TUTORIAL 2.4
Cell Cycle Regulation
OVERVIEW
The events that occur from the completion of one cell division until the beginning of the
next constitute the cell cycle. How is this process, which is fundamentally the same in all
eukaryotic organisms, regulated? This tutorial examines the conditions that must be monitored as a cell proceeds with mitosis and further proliferation.
TEXTBOOK REFERENCES
Interphase and the Cell Cycle (pp. 23-24)
The Duration of the Cell Cycle
The cell cycle, including mitosis, is fundamentally the same in all eukaryotic organisms.
The similarity of the events suggests that the cell cycle is governed by a genetic program
that has been conserved throughout evolution. In part because disruption of this regulation may lead to uncontrolled cell division (cancer), scientists are profoundly interested in
how genes regulate the cell cycle.
In our representative 16-hour cell cycle, about 15 hours will be spent in interphase and
only 1 hour in mitosis.
Of the time in interphase, approximately 5 hours will be spent in the G1 stage of interphase.
Approximately 7 hours will be spent in the S stage of interphase, during which the cell
duplicates its DNA.
Approximately 3 hours will be spent in the G2 stage of interphase.
Only about 1 hour will be spent in mitosis.
Let's examine the hour spent in mitosis.
More than half of mitosis (36 minutes out of 60) is spent in prophase. About 3 minutes are
spent in metaphase, 3 minutes in anaphase, and 18 minutes in telophase.
Cell Cycle Checkpoints
In the cell cycle, the initial interphase stage labeled G1 is of great interest in cell proliferation and its control.
Late in G1, cells follow one of two paths.
At a point late in G1 called the G1/S checkpoint, cells either withdraw from the cell cycle
or become committed to initiating DNA synthesis and completing the cell cycle. If cells
withdraw from the cycle, they typically remain metabolically active but do not proliferate.
They are said to enter the G0 stage.
Some cells enter G0 and never reenter the cell cycle. Other cells can become quiescent in
G0 and then at some later stage be stimulated to reenter the cell cycle. Cancer cells are
characterized by uncontrolled cell division. They apparently never enter G0, or they pass
through it very quickly.
Checkpoints are crucial to the proper functioning of the cell cycle. At these cell cycle checkpoints, the cell evaluates its status and, if all criteria have been met, the cell passes through
the checkpoint to continue the cell cycle.
The critical checkpoints are illustrated schematically in the figure. They are called the
G1/S checkpoint, the G2/M checkpoint, and the M checkpoint.
When the cell leaves mitosis, it enters the G1 stage of interphase. Soon thereafter, a decision is made either to enter the G0 stage or to continue through G1. If the cell commits to
cell division, it grows and is metabolically active until it reaches the G1/S checkpoint.
At the G1/S checkpoint, the cell monitors its size and the state of its DNA. If these properties are satisfactory, the cell progresses past the checkpoint. However, if the cell is too
small or the DNA is damaged, the cell arrests at the G1/S checkpoint until the conditions
are corrected by cell growth or DNA repair.
The cell continues through S, duplicating its DNA. Before entering mitosis, the cell
encounters the G2/M checkpoint. Physiological conditions in the cell are monitored; if
DNA replication or repair to any damaged DNA is not complete, the cell arrests at G2/M
until these tasks are done.
Thus, G2/M prevents the onset of mitosis unless the cell has precisely duplicated, undamaged DNA. If these conditions are satisfied, the cell passes through G2/M and proceeds to
the first steps of mitosis.
The final checkpoint is M, which occurs during mitosis. Here, mitosis arrests unless the
spindle assembly is properly formed and is attached securely to the kinetochores (associated with centromeres). If all is well, the cell passes through the M checkpoint and completes mitosis. The resulting daughter cells begin the cell cycle again.
Checkpoints are crucial to the cell's health. If the G1/S or G2/M checkpoints malfunction,
a cell with damaged DNA could proceed through the cycle and begin a series of uncontrolled divisions; that is, it could become cancerous.
Cell Cycle Summary
To review, the primary functions of the G1/S, G2/M, and M checkpoints are summarized
at left.
The times spent in different parts of the cell cycle vary from species to species and in different types of cells. Many cells, when grown in test tubes (in vitro), have a cell cycle of
approximately 16 hours.
The cell cycle is summarized by these diagrams, which give the basic divisions of the cell
cycle, some typical times spent in each stage of the cycle, and the most important checkpoints in the cycle.
CONCLUSION
The similarity of the events leading to cell proliferation in eukaryotic organisms suggests
that the cell cycle is governed by a genetic program that has been conserved throughout
evolution. The normal cell cycle is tightly regulated at three checkpoints. These checkpoints arrest cell division if they detect damaged DNA, insufficient cell growth, defective
DNA replication, or failure to form mitotic structures. Checkpoints are crucial to the cell's
health because disruption of this regulation could lead to the uncontrolled divisions that
characterize cancer.
YOU
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SHOULD NOW BE ABLE TO
Compare the durations of the different stages of interphase and mitosis.
Explain how cells may exit the cell cycle.
Describe the criteria that are evaluated at each checkpoint.
KEY TERMS
G1/S checkpoint
G2/M checkpoint
interphase
M checkpoint
mitosis