Essential Cell Biology 5th edition

The Cell-Cycle Control System
619
Cdk
cyclin
active
cyclin–Cdk
complex
p27
inactive
p27–cyclin–Cdk
complex
Figure 18−11 The activity of a Cdk can be
blocked by the binding of a Cdk inhibitor.
In this instance, the inhibitor protein (called
p27) binds to an activated cyclin–Cdk
complex. Its attachment prevents the
Cdk from phosphorylating target proteins
required for progress through G 1 into S
phase.
Figure 18–3). At these transitions, the control system monitors the cell’s
internal state and the conditions in its environment, before allowing the
cell to continue through the cycle. For example, it allows entry into S
phase only if environmental conditions are appropriate; it triggers mitosis
only after the DNA has been completely replicated; and it initiates
chromosome segregation only after the duplicated chromosomes are
correctly aligned on the mitotic ECB5 e18.11/18.11 spindle.
To accomplish these feats, the control system uses a combination of the
mechanisms we have described. At the G 1 -to-S transition, it uses Cdk
inhibitors to keep cells from entering S phase and replicating their DNA
(see Figure 18−11). At the G 2 -to-M transition, it suppresses the activation
of M-Cdk by inhibiting the phosphatase required to activate the Cdk (see
Figure 18−10). And it can delay the exit from mitosis by inhibiting the
activation of APC/C, thus preventing the degradation of M cyclin (see
Figure 18−9).
These mechanisms, summarized in Figure 18−12, allow the cell to make
“decisions” about whether to progress through the cell cycle or to arrest
in the current phase and await more favorable conditions. In the next section,
we take a closer look at how the cell-cycle control system decides
whether a cell in G 1 should commit to divide.
DNA replication
not complete
DNA
damage
chromosomes not
properly attached
to spindle
INHIBITION OF ACTIVATING
PHOSPHATASE (Cdc25) BLOCKS
ENTRY TO MITOSIS
INHIBITION OF APC/C
ACTIVATION DELAYS
EXIT FROM MITOSIS
M
G 2
CONTROLLER
S
G 1
Cdk INHIBITORS BLOCK
ENTRY TO S PHASE
environment not
favorable
Figure 18−12 The cell-cycle control
system uses various mechanisms to pause
the cycle at specific transition points.