Essential Cell Biology 5th edition

622 CHAPTER 18 The Cell-Division Cycle
Figure 18−15 DNA damage can arrest the
cell cycle in G 1 . When DNA is damaged,
specific protein kinases respond by both
activating the p53 protein and halting its
otherwise rapid degradation. Activated p53
protein thus accumulates and stimulates
the transcription of the gene that encodes
the Cdk inhibitor protein p21. The p21
protein binds to G 1 /S-Cdk and S-Cdk and
inactivates them, so that the cell cycle
arrests in G 1 .
p53
DNA
X-RAYS DAMAGE DNA
ACTIVATION OF PROTEIN KINASES
THAT PHOSPHORYLATE p53,
STABILIZING AND ACTIVATING IT
P
stable,
activated p53
IN ABSENCE OF
DNA DAMAGE,
p53 IS DEGRADED
IN PROTEASOMES
P
ACTIVE p53 BINDS TO
REGULATORY REGION
OF p21 GENE
p21 gene
TRANSCRIPTION
TRANSLATION
p21 mRNA
p21 (Cdk
inhibitor protein)
ACTIVE
G 1/S-Cdk
and S-Cdk
INACTIVE
G 1 /S-Cdk and S-Cdk
complexed with p21
damaged DNA. They can also withdraw from the cell cycle for prolonged
periods—either temporarily or permanently.
QUESTION 18–4
What might be the consequences
if a cell replicated damaged DNA
before repairing it?
The most radical decision that the cell-cycle control system can make
is to withdraw the cell from the cell cycle permanently. This decision
has a special importance in multicellular organisms. Many cells in the
human body permanently stop dividing when they differentiate. In such
terminally differentiated cells, such as nerve or muscle cells, the cell-cycle
control system is dismantled completely and genes encoding the relevant
cyclins and Cdks are irreversibly ECB5 e18.15/18.15 shut down.
In the absence of appropriate signals, other cell types withdraw from
the cell cycle only temporarily, entering an arrested state called G 0 . They
retain the ability to reassemble the cell-cycle control system quickly and
to divide again. Most liver cells, for example, are in G 0 , but they can be
stimulated to proliferate if the liver is damaged.
Much of the diversity in cell-division rates in the adult body lies in the variation
in the time that cells spend in G 0 or in G 1 . Some cell types, including
liver cells, normally divide only once every year or two, whereas certain
epithelial cells in the gut divide more than twice a day to renew the lining
of the gut continually. Many of our cells fall somewhere in between: they
can divide if the need arises but normally do so infrequently.