This podcast provides an overview of mitosis. The next several slides come
from the Alberts textbook. What we show here on the left would be interphase and
then M phase. Now, this is just exaggerated showing the M phase and
simply so the artists could get all the labels in. You know, of course, the interphase
is the longest part of the cell cycle and M phase or the division phase is the
shorter phase of the cell cycle. During interphase the cell increases in size,
DNA of the chromosomes is replicated, and importantly, the centrosome is duplicated
and that's what's being shown here. At prophase, the replicated chromosomes each
are going to consist of two closely associated sister chromatids condense.
This condensation of chromosomes depends on phosphorylation of histone H1 and on
phosphorylation of molecules called condenseins and cohesins. And you would
have talked about histones, condenseins and cohesins in biochemistry. Outside of
the nucleus, the mitotic spindle is going to begin to assemble between the
centrosomes which have replicated and have begun to move apart. This assembly
of the spindles depends on phosphorylation of micro tubular
associated proteins at the micro tubular organizing center. Prometaphase starts
abruptly with a breakdown of the nuclear envelope and that breakdown occurs
because of phosphorylation of nuclear lamins. And you may remember, there are
three groups of nuclear lamins: lamin A, lamin B, and lamin C and these are
on the inner face of the nuclear envelope. They help to hold the nuclear
envelope integrity together and they also may serve as attachment sites for
chromosomes during interphase, not only for DNA replication but for
transcriptional activity. At any point, once the nuclear envelope
is broken down, chromosomes can now attach to spindle microtubules by their
kineti chords and they'll begin to undergo very active movement. In humans,
progression from prophase through prometaphase is under the control of
cyclin B- Cdk1. This is the so-called mitotic cyclin cyclin-dependent kinase or, in historic
terms, it's human MPF. I just want to remind you that centriole replication is
synchronized in the cell cycle such that each replicated pair of centrioles is
going to elaborate microtubules for the mitotic spindle under the influence of
cyclin B-Cdk1. And in this part of the diagram, you can see that the spindles
have replicated and they're beginning to move apart in early prophase and in
prophase so that by the time the nuclear envelope is broken down the spindle is
forming at metaphase and the centrioles are on opposite poles of where the
nucleus would be. In animal cells, of course, we see the distinct centriole
pairs. We know that plant cells don't have centrioles, yet they undergo mitosis
perfectly well. So, the spindle fibers originate from the microtubule
organizing center in the plant cells even though they're not well-defined
centrioles. At metaphase, the chromosomes are aligned at the equator of the
spindle midway between the spindle poles. The paired kinetochore microtubules on
each side of the chromosome attach to opposite spindle poles and then at
anaphase the paired chromatids are synchronously separated each is pulled
slowly towards the spindle pole that it faces. The kinetochore microtubules get
shorter and the spindle poles are also pushed apart. And so pulling of the
on the spindle and pushing the spindle poles apart both contribute to
chromosome separation. During telophase the two sets of daughter chromosomes arrive
at the poles of the spindle, a new nuclear envelope is going to reassemble
around each chromosome set completing the formation of two nuclei and marking
the end of mitosis. The division of the cytoplasm begins with the assembly of
the contractile ring. During cytokinesis, in an animal cell, the cytoplasm is
divided in two by the contractile ring and the contractile ring consists of
actin and myosin and as you know, that pinches the cell into two daughter cells.
As the cell has divided, there's going to be the reformation of the interphase
array of microtubules and those microtubules are going to be assembled
by nucleation at the microtubule organizing center which is of course the
centrosome and that's going to be occurring now in each daughter cell. The
images that I've shown on the side like these images or if I go back a couple of
slides these images, these are time-lapse micro cinematography images, stills from
time-lapse and they were just showing cell division in an amphibian. And so,
it's just showing that in this particular amphibian the entire mitotic
time took 362 minutes. One thing I do want to remind you of during the M
phase of the cell cycle, the micro tubular cytoskeleton has dramatically
altered and that's going to, of course, get re-established once the chromosomes have
divided and the nuclei have divided. We understand there are three classes of
microtubules. There are astral microtubules that radiate from the micro
tubular organizing center and they radiate out
towards the cortical cytoskeleton, and that's what would be shown like this or
like this. There are polar microtubules that emanate from the centriole and they
find microtubule that are emanating from the opposite
centriole, and the little black circles that are shown here are meant to
represent microtubule motors and these microtubule motors play an important
role in movement of the spindle. And then, of course, there are kinetochore
microtubules that are emanate in the centrioles and attach onto the
kinetochore in the chromosomes. Movement of chromosomes results from an interplay
of spindle microtubules and micro tubular motor proteins and from spindle
microtubules and cytoskeleton actin fibers. This micrograph just shows the
spindle poles, you can actually see a cross-section and a longitudinal section
of one of the pairs of centrioles and you can see the microtubules going
towards the kinetochores and the chromosomes. Unless you think that it's
only one microtubule going to each kinetochore, it's clear there are
multiple microtubules attaching to each kinetochore on each chromosome. At
anaphase A chromosomes are pulled poleward. There's a shortening of
kinetochore microtubules. The forces generated at the kinetochores move the
daughter chromosomes toward the spindle poles. So, in anaphase A the daughter
chromosomes are pulled towards opposite poles, as the kinetochore microtubules
depolymerize. And this is a little bit counterintuitive, because what happens is
these kinetochore microtubules in prometaphase are going in and out, they're
polymerizing, depolymerizing very rapidly, trying to find their target, their target
being the kinetochore of the chromosome. Once they hit that target kinetochore
they get stabilized. The chromosomes move to the opposite poles as the spindles
depolymerizing and they're depolymerizing at the kinetochore. So, they're getting
shorter, as they get shorter the chromosome
moves towards the spindle pole. At anaphase B the spindle poles are pushed
apart due to elongation and sliding of polar microtubules past each other and
these are with kinesan motors that are moving in opposite directions on the
microtubules and they're also pulled apart as the astral microtubules
interact with the quadrifocal cytoskeleton. So, in anaphase B there's a
pushing of the spindle poles apart and there's a pulling of the spindle poles apart.