Essential Cell Biology 5th edition

634 CHAPTER 18 The Cell-Division Cycle
Figure 18−28 APC/C triggers the
separation of sister chromatids by
promoting the destruction of cohesins.
APC/C indirectly triggers the cleavage of
the cohesins that hold sister chromatids
together. It catalyzes the ubiquitylation and
destruction of an inhibitory protein called
securin, which blocks the activation of a
proteolytic enzyme called separase. When
freed from securin, separase cleaves the
cohesin complexes, allowing the mitotic
spindle to pull the sister chromatids apart.
active APC/C
inhibitory
protein
(securin)
inactive
proteolytic
enzyme
(separase)
UBIQUITYLATION AND
DEGRADATION OF
SECURIN
mitotic
spindle
cohesin
complex
active
separase
cleaved and
dissociated cohesins
metaphase
anaphase
QUESTION 18–6
If fine glass needles are used to
manipulate a chromosome inside a
living cell during early M phase, it
is possible to trick the kinetochores
on the two sister chromatids into
attaching to the same spindle
pole. This arrangement is normally
unstable, but the attachments can
be stabilized if the needle is used
to gently pull the chromosome so
that the microtubules attached to
both kinetochores (via the same
spindle pole) are under tension.
What does this suggest to you
about the mechanism by which
kinetochores normally become
attached and stay attached to
microtubules from opposite spindle
poles? Is the finding consistent with
the possibility that a kinetochore
is programmed to attach to
microtubules from a particular
spindle pole? Explain your answers.
Chromosomes Segregate During Anaphase
Once the sister chromatids separate, they all move toward the spindle
poles at the same speed, which is typically about 1 μm per minute. The
movement is the consequence of two independent and overlapping processes
that rely on different parts of the mitotic spindle. In anaphase A,
the kinetochore microtubules shorten and the attached chromosomes
move poleward. In anaphase B, the spindle poles themselves move apart,
further segregating the two sets ECB5 of e18.28/18.28
chromosomes (Figure 18−29).
The driving force for the movements of anaphase A is thought to be
provided mainly by the loss of tubulin subunits from both ends of the
kinetochore microtubules. The driving forces in anaphase B are thought
to be provided by two sets of motor proteins—members of the kinesin
and dynein families—operating on different types of spindle microtubules
(see Figure 17−19A). Kinesin proteins act on the long, overlapping interpolar
microtubules, sliding the microtubules from opposite poles past
one another at the equator of the spindle and pushing the spindle poles
apart. Dynein proteins, anchored to the plasma membrane, move along
astral microtubules to pull the poles apart (see Figure 18−29B).
An Unattached Chromosome Will Prevent Sister-
Chromatid Separation
If a dividing cell were to begin to segregate its chromosomes before all
the chromosomes were properly attached to the spindle, one daughter
cell would receive an incomplete set of chromosomes, while the other
would receive a surplus. Both situations could be lethal. Thus, a dividing
cell must ensure that every last chromosome is attached properly to the
spindle before it completes mitosis. To monitor chromosome attachment,
the cell makes use of a negative signal: the kinetochores of unattached
chromosomes send a “stop” signal to the cell-cycle control system. This
signal inhibits further progress through mitosis by blocking the activation
of APC/C (see Figure 18−28). Without active APC/C, the sister chromatids