Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

992 Chapter 17: The Cell Cycle
(A)
spindle
pole
CUT WITH
LASER
arm without
kinetochore moves
away from pole
arm with
kinetochore moves
toward pole
(B)
interpolar
or astral
microtubule
+
kinetochore
microtubule
plus-end-directed
kinesin-4,10
motor proteins
+
PUSH
from the pole. The switch between the two states may depend on the degree of
tension in the kinetochore. It has been proposed, for example, that, as chromosomes
move toward a spindle pole, an increasing polar ejection force generates
tension in the kinetochore nearest the pole, triggering a switch to the away-fromthe-pole
state and gradually resulting in the accumulation of chromosomes at the
equator of the spindle.
–
–
PULL
Figure 17–36 How opposing forces may
drive chromosomes to the metaphase
plate. (A) Evidence for a polar ejection
force that pushes chromosomes away
from the spindle poles toward the spindle
equator. In this experiment, a laser beam
severs a prometaphase chromosome
that is attached to a single pole by a
kinetochore microtubule. The part of
the severed chromosome without a
kinetochore is pushed rapidly away
from the pole, whereas the part with
the kinetochore moves toward the pole,
reflecting a decreased repulsion. (B) A
model of how two opposing forces may
cooperate to move chromosomes to the
metaphase plate. Plus-end-directed motor
proteins (kinesin-4 and kinesin-10) on the
chromosome arms are thought to interact
with microtubules to generate the polar
ejection force, which pushes chromosomes
toward the spindle equator (see Figure
17–25). Poleward forces generated by
depolymerization at the kinetochore,
together with microtubule flux, are thought
to pull chromosomes toward the pole.
The APC/C Triggers Sister-Chromatid Separation and the
Completion of Mitosis MBoC6 m17.42/17.36
After M-Cdk has triggered the complex processes leading up to metaphase, the
cell cycle reaches its climax with the separation of the sister chromatids at the
metaphase-to-anaphase transition (Figure 17–37). Although M-Cdk activity sets
the stage for this event, the anaphase-promoting complex (APC/C) discussed earlier
throws the switch that initiates sister-chromatid separation by ubiquitylating
several mitotic regulatory proteins and thereby triggering their destruction (see
Figure 17–15A).
During metaphase, cohesins holding the sister chromatids together resist the
poleward forces that pull the sister chromatids apart. Anaphase begins with the
sudden loss of sister-chromatid cohesion, which allows the sisters to separate
and move to opposite poles of the spindle. The APC/C initiates the process by
targeting the inhibitory protein securin for destruction. Before anaphase, securin
(A)
20 µm
(B)
Figure 17–37 Sister-chromatid separation at anaphase. In the transition from metaphase (A) to anaphase (B), sister chromatids suddenly
and synchronously separate and move toward opposite poles of the mitotic spindle—as shown in these light micrographs of Haemanthus (lily)
endosperm cells that were stained with gold-labeled antibodies against tubulin. (Courtesy of Andrew Bajer.)