Wednesday, November 11, 2015

Cell Cycle Control

I have spoken about the cell cycle in previous posts. Now it's time to explain how the cell cycle is controlled!

Know the meanings and importance of the key words.

Homeostasis- Maintenance of a stable condition. For example, in the body, temperature and pH are maintained at a certain level.
Cell cycle checkpoints- Points in the cell cycle where the cell "checks" to make sure that everything is okay before proceeding on to the next stage. Once the cell passes a checkpoint, it cannot go back.
Cyclin- A protein that binds to a cyclin-dependent kinase (Cdk) in order to regulate their function. There are different types of cyclins that are produced at different stages of the cell cycle.
Cyclin dependent kinase (Cdk)- A kinase (i.e. an enzyme that adds phosphate groups to proteins) that needs to be bound to a cyclin in order to function. Cdk levels remain constant throughout the cell cycle, but the proteins that they phosphorylate differ according to which cyclin is bound to the Cdk.
p53, a tumour suppressor- p53 is essentially a protein that either tells the cell not to replicate the DNA if there are some mismatches or to commit suicide if the DNA is severely damaged. (What a bully, picking on damaged cells like that.) It works by recognising DNA mismatches and then activating other proteins. In the case of a smaller amounts of damage, p53 activates p21, which stops Cdks from phosphorylating their target proteins, which in turn prevents entry into the S phase until the DNA is repaired. In the case of larger amounts of damage, p53 activates genes that code for apoptosis (see my previous post for more information on apoptosis).

Have an understanding of the cell cycle phases and the checkpoints where control is exerted.

I think I've already gone over the cell cycle before, but now seems like a good time to go over it again.

The first stage of the cell cycle is the G1 phase, in which cells do most of their growing and stuff. Some cells leave the cell cycle at this point and enter the G0 phase, where they remain pretty much stable for the rest of their lives. (Neurons and skeletal muscle cells are prime examples.) Cells that are destined to divide pass through the first checkpoint: the G1/S checkpoint, also known as Start. At this point, the cell ensures that the DNA is intact and that other environmental conditions are favourable for division. If everything is good, the cell proceeds on to the S phase.

In the S phase, the cell replicates its DNA. Once that is finished, the cell is said to be in the G2 phase, during which it undergoes a little more growth. At the end of this stage, there is another checkpoint: the G2/M checkpoint. At this stage, the cell checks to ensure that DNA replication has been completed properly.

Finally, the cell undergoes the M phase, otherwise known as the mitotic phase. I have written about the stages of the mitotic phase in an earlier post. Between metaphase and anaphase, there is another checkpoint, known as the spindle assembly checkpoint. At this stage, the cell checks to make sure that the spindle fibres have formed properly and are attached to the chromosomes.

Understand that cyclin levels oscillate with cycle phase.

As I mentioned in the definitions, cyclins are proteins that bind to and activate cyclin-dependent kinases (Cdks). Cyclins also determine which proteins a Cdk will phosphorylate. If I remember correctly, often a cyclin bound to a Cdk will activate the production of the next cyclin needed. For example, G1/S-cyclins needed to pass through Start will stimulate the production of S-cyclins, which are needed for the events that take place during DNA replication.

Realise that Cdk activity is controlled by cyclin binding, phosphorylation and inhibitors.

As also mentioned in the definitions, Cdks require cyclins to activate them (hence they are cyclin dependent kinases). Like all kinases, Cdks work by adding phosphate groups to their target proteins. Cdks themselves can also be activated or inactivated by the addition of phosphate groups.

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