Lecture 15 - Mitosis

M for mitosis
 Mitosis is the process that partitions
replicated chromosomes equally to 2
daughter cells
Mitosis proceeds through 6 stages

Cytokinesis
 Successful mitosis requires the precise
coordination of many processes

•  Packaging of the genome into mitotic chromosomes

•  Regulation of microtubules and motors to build
spindle
•  Disassembly of the nuclear membrane
•  Attachment and movement of chromosomes on the
spindle
•  Cleavage of a cell into 2 daughters
Interphase - late G2

•  DNA is duplicated
•  Cell has doubled in
size
•  Centrosome has
duplicated
•  M-cyclin levels high
Prophase
•  Chromosomes
condense
•  Nuclear envelope
breaks down
•  Microtubules
reorganize to make
asters
•  Centrosomes move to
opposite sides of the
cell
 Replicated chromosomes are prepared
for segregation by cohesins and
condensins

•  Cohesins hold sister

chromatids together
•  Cohesins are deposited
on chromosomes
during S-phase
Replicated chromosomes are prepared for
segregation by cohesins and condensins

•  Condensins bind to chromosomes in prophase

•  Molecular motors that wind chromatin into small physical
packets for mitosis
 The nuclear envelope breaks
down and re-forms during mitosis
 Dynamics of the nuclear
envelope during cell division
Prometaphase
•  Chromosomes are
captured by microtubules
at the kinetochore
•  Chromosomes undergo
active movement
oscillating back and forth
on the spindle
•  Kinetochores of each
sister chromatid captured
by microtubules from each
pole
 Centrosomes organize the
microtubules in a mitotic spindle
Microtubules are the core structural
component of the mitotic spindle
Changes in microtubule dynamics
contribute to spindle assembly

Interphase Mitosis
Growth rate Intermediate Low
Shrinkage rate Intermediate High
Frequency of
Low High
catastrophe
Three sets of microtubules make up the
mitotic spindle
Bipolar spindles are formed by the selective
stabilization of interacting microtubules

•  Microtubules grow in
random directions
•  Overlapping
microtubules from
opposite poles are
cross-linked and
stabilized by MAPs and
motor proteins
 Microtubule dynamics are regulated by
associated proteins
•  Microtubule-associated proteins (MAPs) stabilize
microtubules in interphase, but are phosphorylated in
mitosis and decrease their stabilizing effects

•  Catastrophins are proteins that destabilize

microtubules, their activity is upregulated upon entry
into mitosis
Kinetochores attach chromosomes to the
mitotic spindle
Capture of centrosome microtubules by
kinetochores
Metaphase
•  Chromosome
congression to the
metaphase plate
•  Paired kinetochore
microtubules on each
chromosome are
attached to opposite
poles of the spindle
•  Mitotic checkpoint
ensures the fidelity of
this bi-polar attachment
Unattached kinetochores mediate the
mitotic checkpoint
 Checkpoint: spindle assembly

•  Mitosis must not complete unless all the

chromosomes are attached to the mitotic
spindle
•  Mitotic checkpoint delays metaphase to
anaphase transition until all chromosomes
are attached
•  Prolonged activation of the checkpoint -->cell
death
•  Mechanism of many anti-cancer drugs
Anaphase
•  M-cyclin is destroyed
•  Paired chromatids
simultaneously separate
to form 2 daughter
chromosomes
•  Each chromosome is
pulled to the pole to which
it is attached
•  Kinetochore MTs shorten
- anaphase A movement
•  Spindle elongates -
anaphase B movement
APC triggers the separation of sister chromatids
by tagging cohesins for destruction
Anaphase chromosome movement is driven
by 2 processes
Spindle elongation during anaphase B is
mediated by motor proteins
Microtubule attachment sites in a kinetochore
are thought to form a sliding collar
 Kinetochore movement at the
metaphase-to-anaphase transition
Telophase
•  The 2 sets of
chromosomes arrive at
the spindle pole and
begin to decondense
•  Nuclear envelope begins
to reform
•  Cleavage furrow begins to
form around
circumference of the
middle of the 2 daughter
cells
Cytokinesis
•  The division of the
cytoplasm is
completed by the
contractile ring
•  Cells re-enter
interphase in G1
•  Microtubules reform
their interphase
organization
Cytokinesis is the process by which
the cytoplasm is cleaved in two

The cleavage furrow of the plasma membrane is

formed by the action of the contractile ring.
The contractile ring divides the
cell in two
 Organelles are segregated to
each daughter cell during mitosis
Golgi apparatus partitioning
during mitosis