Essential Cell Biology 5th edition

M Phase
625
Figure 18−17 Activated M-Cdk indirectly activates more
M-Cdk, creating a positive feedback loop. Once activated,
M-Cdk phosphorylates, and thereby activates, more Cdk-activating
phosphatase (Cdc25). This phosphatase can now activate more M-Cdk
by removing the inhibitory phosphate groups from the Cdk subunit.
M-Cdk Drives Entry into Mitosis
One of the most remarkable features of the cell-cycle control system is
that a single protein complex, M-Cdk, brings about all the diverse and
intricate rearrangements that occur in the early stages of mitosis. Among
its many duties, M-Cdk helps prepare the duplicated chromosomes for
segregation and induces the assembly of the mitotic spindle—the machinery
that will pull the duplicated chromosomes apart.
M-Cdk complexes accumulate throughout G 2 . But this stockpile is not
switched on until the end of G 2 , when the activating phosphatase Cdc25
removes the inhibitory phosphates holding M-Cdk activity in check. This
act of activation is self-reinforcing: once activated, each M-Cdk complex
can indirectly turn on additional M-Cdk complexes—by phosphorylating
and activating more Cdc25 (Figure 18−17). Activated M-Cdk also shuts
down the inhibitory kinase Wee1 (see Figure 18−10), further promoting
the production of activated M-Cdk. The overall consequence is that, once
M-Cdk activation begins, it ignites an explosive increase in M-Cdk activity
that drives the cell abruptly—and irreversibly—from G 2 into M phase.
The same M-Cdk complexes that drive entry into mitosis also help set the
stage for its exit. Activated M-Cdk turns on APC/C, which—after a period
of delay—directs the destruction of M cyclin and, ultimately, the inactivation
of M-Cdk.
Cohesins and Condensins Help Configure Duplicated
Chromosomes for Separation
To ensure that duplicated chromosomes will be properly separated during
mitosis, two related protein complexes help cells manage and keep
track of the replicated DNA. The first complexes come into play during
S phase. When a chromosome is duplicated, the two copies remain tightly
bound together. These identical copies—called sister chromatids—each
contain a single, double-stranded molecule of DNA, along with its associated
proteins. The sisters are held together by protein complexes called
cohesins, which assemble along the length of each chromatid as the
DNA is replicated. This cohesion between sister chromatids is crucial
for proper chromosome segregation, and it is broken completely only in
late mitosis to allow the sisters to be pulled apart by the mitotic spindle.
Defects in sister-chromatid cohesion lead to major errors in chromosome
segregation. In humans, such mis-segregation can lead to abnormal
numbers of chromosomes, resulting in genetic imbalances that are usually
deleterious or even lethal.
When the cell enters M phase, the duplicated chromosomes condense,
becoming visible under the microscope. Protein complexes called
condensins help carry out this chromosome condensation, which
reduces mitotic chromosomes to compact bodies that can be more easily
segregated within the crowded confines of the dividing cell. The assembly
of condensin complexes onto the DNA is triggered by the phosphorylation
of condensins by M-Cdk.
Cohesins and condensins are structurally related, and both are thought
to form ring structures around chromosomal DNA. However, whereas
cohesins encircle the two sister chromatids, tying them together (Figure
18−18A), condensins assemble along each individual sister chromatid,
inactive
Cdc25
phosphatase
active
Cdc25
phosphatase
inhibitory
phosphates
P
P
inactive
M-Cdk
P
2 P
active
M-Cdk
ECB5 E18.17/18.17
QUESTION 18–5
POSITIVE
FEEDBACK
A small amount of cytoplasm
isolated from a mitotic cell is
injected into an unfertilized frog
oocyte, causing the oocyte to
enter M phase (see Figure 18−7A).
A sample of the injected oocyte’s
cytoplasm is then taken and injected
into a second oocyte, causing this
cell also to enter M phase. The
process is repeated many times
until, essentially, none of the original
protein sample remains, and yet,
cytoplasm taken from the last in the
series of injected oocytes is still able
to trigger entry into M phase with
undiminished efficiency. Explain this
remarkable observation.