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

984 Chapter 17: The Cell Cycle
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dynein
kinesin-14
spindle microtubule
kinesin-5
+
+
–
+
– –
– – –
–
+ centrosome
dynein
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Figure 17–25 Major motor proteins of the
spindle. Four major classes of microtubuledependent
motor proteins (yellow boxes)
contribute to spindle assembly and function
(see text). The colored arrows indicate the
direction of motor protein movement along
a microtubule—blue toward the minus end
and red toward the plus end.
plasma
membrane
kinesin-4,10
sister chromatids
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proteins, also called chromokinesins, are plus-end directed motors that associate
with chromosome arms and push the attached chromosome away from the pole
(or the pole away from the chromosome). Finally, dyneins are minus-end directed
motors that, together with associated proteins, organize microtubules at various
locations in the cell. They link MBoC6 the plus m17.30/17.25 ends of astral microtubules to components
of the actin cytoskeleton at the cell cortex, for example; by moving toward the
minus end of the microtubules, the dynein motors pull the spindle poles toward
the cell cortex and away from each other.
Multiple Mechanisms Collaborate in the Assembly of a Bipolar
Mitotic Spindle
The mitotic spindle must have two poles if it is to pull the two sets of sister chromatids
to opposite ends of the cell in anaphase. In most animal cells, several mechanisms
ensure the bipolarity of the spindle. One depends on centrosomes. A typical
animal cell enters mitosis with a pair of centrosomes, each of which nucleates
a radial array of microtubules. The two centrosomes provide prefabricated spindle
poles that greatly facilitate bipolar spindle assembly. The other mechanisms
depend on the ability of mitotic chromosomes to nucleate and stabilize microtubules
and on the ability of motor proteins to organize microtubules into a bipolar
array. These “self-organization” mechanisms can produce a bipolar spindle even
in cells lacking centrosomes.
We now describe the steps of spindle assembly, beginning with centrosomedependent
assembly in early mitosis. We then consider the self-organization
mechanisms that do not require centrosomes and become particularly important
after nuclear-envelope breakdown.
Centrosome Duplication Occurs Early in the Cell Cycle
Most animal cells contain a single centrosome that nucleates most of the cell’s
cytoplasmic microtubules. The centrosome duplicates when the cell enters the
cell cycle, so that by the time the cell reaches mitosis there are two centrosomes.
Centrosome duplication begins at about the same time as the cell enters S phase.
The G 1 /S-Cdk (a complex of cyclin E and Cdk2 in animal cells; see Table 17–1) that
triggers cell-cycle entry also helps initiate centrosome duplication. The two centrioles
in the centrosome separate, and each nucleates the formation of a single
new centriole, resulting in two centriole pairs within an enlarged pericentriolar
matrix (Figure 17–26). This centrosome pair remains together on one side of the
nucleus until the cell enters mitosis.
There are interesting parallels between centrosome duplication and chromosome
duplication. Both use a semiconservative mechanism of duplication, in
which the two halves separate and serve as templates for construction of a new
half. Centrosomes, like chromosomes, must replicate once and only once per
cell cycle, to ensure that the cell enters mitosis with only two copies: an incorrect
number of centrosomes could lead to defects in spindle assembly and thus errors
in chromosome segregation.