Monday, April 29, 2013

In as many words as possible, explain 'normal' regulation of the cell cycle in eukaryotes?Include checkpoints, cyclins, CDKs, etc. in your answer.

The cell cycle is regulated at various checkpoints in the
cycle.  At these checkpoints a sensor mechanism is responsible for analyzing the DNA 
for damage and it either gets repaired or the cell is destroyed.  A signal mechanism is
responsible for this step. Finally, an effector mechanism is responsible for stalling
the cell cycle or for the destruction of the cell.  During the G1 phase, the RP or
restriction checkpoint is when just before entering the S or synthesis phase, it is
determined whether the cell should divide, delay mitosis or enter the resting phase. If
conditions are not possible for cell division, the cell may stay in the Go phase, which
is a resting state. The restriction point is  controlled by the action of CDK inhibitor
p16, which inhibits the CDK4/6 causing it to no longer interact with cyclin D1, which is
responsible for allowing the cell cycle to proceed. When growth is induced, the
expression of this cyclin is high and they do bind which in turn stops the transcription
factor E2F from being inhibited. As this occurs, cyclin E can be expressed. This in
turn, interacts with CDK2 and allows for the cell to proceed to the Go-G-S
transition.  At the next checkpoint, or at the end of the G2 phase, the start of mitosis
will be initiated.  The CDK's at this checkpoint are activated when the CDK is
phosphorylated. This is because of MPF, which is mitosis promoting factor. This factor
will allow the DNA to begin replication. This is necessary because after mitosis, the
two daughter cells will each need a complete copy of the DNA. The phosphatase called
Cdc25 removes inhibitory phosphates in the MPF complex. This will occur only if the DNA
is not damaged. The next checkpoint is called the mitotic spindle checkpoint. This
occurs during mitosis at metaphase. During metaphase, the chromosome pairs or sister
chromatids line up in the middle of the cell. They should be under bipolar tension. This
tension is sensed and initiates the entry into the next step in mitosis known
as anaphase. Cyclin B is degraded and this allows the cell to progress into anaphase. 
Next, the anaphase promoting complex is no longer inhibited. This in turn allows the
breakdown of securin. This protein inhibits separase, which is responsible for the
separation of the sister chromatids. Finally, the cells splits into two daughter cells
and the cells will enter G1 again. The entire process of the cell cycle is like falling
dominoes. As one step occurs, it triggers the next and so on.

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