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Cell Division Lecture 19
Mitotic Phase- Includes Both Mitosis (Nuclear Division) and Cytokinesis (Cytoplasmic)
Division. About 1 hour out of the 24 hour cell cycle process. Goal of Cell Division is to
produce two identical Daughter cells. S phase involves DNA synthesis and duplication of
centrosome. By G2 this should be completed and chromosomes will begin to condense.
Duplicated Centrosomes are adjacent.
G2 to M transition: Requires Active M-CDK- M-CDK activity requires M- Cyclin,
which is increasing due to transcription. Formation of M-CDK complexes is occurring,
however, they are held inactive by inhibitory phosphates that are present. Provided DNA
replication is complete, at G2  M transition activating phosphatase will remove
phosphate. M-CDK can activate positive feedback loop upon activation to further
increase the amount of Active M-CDK- Results in explosive increase in active M-CDK
levels. M-CDK phosphorylates targets necessary for changes that must occur in order for
mitosis to occur.- Initiation of Chromosome Condensation- through phosphorylation of
condensins, Assembly of Mitotic Spindle- phosphorylation of MAPs and catastrophins
that influence Microtubule stability, and Nuclear Envelope Breakdown, through
phosphorylation of intermediate filaments (Lamins) .
Prophase: Individual Replicated Chromosomes condense. Sister chromatids ( 2 per
chromosome) are held together by cohesion complexes. The nucleoli disappear. The
Spindle is composed of centrosomes and the microtubules that extend from them. The
radial arrays of shorter microtubules that extend from the centrosomes are called asters.
The centrosomes move away from each other, apparently propelled by lengthening
microtubules. Kinetochores forms on centromeres of duplicated chromosome.
Prometaphase: The nuclear envelope fragments, and microtubules from the spindle
interact with the condensed chromosomes. Phosphorylation of lamins by M-CDK drives
nuclear envelope fragmentation. Microtubules from each pole can now enter nuclear area
and attach to kinetochores. Polar microtubules arise from opposite ends of the spindle
and interact with one another through crosslinking proteins
Metaphase- Chromosomes are at maximal condensation and the MTs Pull and Push the
sister chromatids until they are all arranged at the metaphase plate, an imaginary plane
equidistant from the poles.
Anaphase The centromeres divide, separating the sister chromatids. Requires M-CDK
activation of Anaphase Promoting Complex (APC), a regulated and specific ubiquitin
ligase. If all chromosomes are not attached to mitotic spindle- even though M-CDK has
activated APC (indirectly) it will be held inactive until all attached. Once okay- APC will
target Securin protein, an inhibitory protein that sequesters Separase. Once degraded,
Separase is now free to go and cleave the Cohesin proteins, releasing sister chromatids.
Movement of chromosomes described as Anaphase A and Anaphase B types. A depends
upon chromosomes being pulled by their centromeres to the minus end of the spindle
pole. Requires Minus End directed Motor Proteins(cytoplasmic dynein). As chromosome
is moving- the MT is depolymerizing at the plus end. The Anaphase B type movement
involves motor proteins associated with the plus end of polar MT. Force spindles apart
from each other, polymerization of plus end of the MT also occurring. Also Astral MT
motor proteins- Minus end directed – attach to the cell cortex and plus end of Astral MTExert outward pull on the spindle. Spindle increases in length..
Telophase: By the end of anaphase, the two poles have equivalent collections of
chromosomes. Now daughter nuclei begin to form at the two poles. Degradation of MCyclin critical for reversal of effects that led to mitosis. Nuclear envelopes arise from the
fragments of the parent cell’s nuclear envelope and other portions of the endomembrane
system. The chromosomes become less tightly coiled.
Cytokinesis, division of the cytoplasm, is usually initiates during anaphase- once sister
chromatids separate. In animal cells, cytokinesis involves the formation of a cleavage
furrow, which pinches the cell in two. Requires a Contractile Ring formed from Actin
and Myosin II filaments.