How Is the Eukaryotic Cell Cycle Regulated?

[Another God]

OK, i need to know everything about the Eukaryotic Cell Cycle : In detail. So this is whereI am going to post what I learn as I go, and where any of you lovely people can post stuff that you know that you think might help me

If you have any links to good cell cycle websites, then feel free to post!

Now let's get cycling...

(PS: I will have an exam question on this topic in about 3 days, the question will be along the lines of:
*Describe the phases of the Eukaryotic cell cycle and the mechanisms that regulate its movement through them
*Give an example of how cancer can arise due to disruption of one of them)

 

[Another God]

http://www.med.unibs.it/~marchesi/cellcycle.gif
This image shows the basic Euk. Cell Cycle.

Often separated into M Phase and Interphase, Interphase actually consists of G₁ phase, S phase and G₂ phase.

The G phases are Gap phases, and not all cells go through them. They are basically thought to be phases of growth, where the cell prepares for DNA and protein Synthesis in G₁ and for division in G₂. Obviously the S Phase is where DNA and protein Synthesis takes place, and the M phase is where division occurs (Mitosis or Meiosis).

During G₁ phase, some cells mey exit the cell cycle and enter the G₀ phase, where it is quiescent, neither growing, synthesising or dividing. It may stay there for days, weeks or years.

Next post I will (or someone else if they want to beat me to it show exactly what it is within the cell that changes to regulate the movement of the cell through these phases. What causes a cell to move through the processes of any given phase? What causes a cell to move into the next phase? What may cause a cell to stop movement through its current phase? What exactly changes as each phase progresses? How can changes in any of these things reult in cancer?

 

[Monique]

Great idea, maybe I should do something similar.. first I'll have to find the time to read my textbook (juggling work and study..)

 

[Another God]

OK, this is how it goes:
Typical Vertebrate Cell Cycle

Passage through the cell cycle is mediated primarily by CDK's (Cyclin Dependent Kinase) and Cyclins.

G₁ phase is pushed towards S phase initially by Cyclin D bound to either CDK4 or CDK6. Amongst all of the other effects of these two complexes, one is the initiation of transcription of Cyclin E, which complexes with CDK2 forming the G₁/S-Cyclin. This CDK2-Cyclin E complex pushes the cell cycle through into the beginning of S phase as Cyclin D-CDK4/6 complex are degraded. Shortly after the cell enters S phase though, Cyclin E is degraded and CDK2 is now complexed to Cyclin A, forming the S-cyclin. This Cyclin mediates all of the S phase tasks, such as appropriate protein synthesis and DNA replication, lasting until the very end of S phase where CDK2 is inactivated and CDK1 takes over, complexing with Cyclins A or B forming the M-Cyclin.

The M-Cyclin, like the other cyclins, phosphorylates its own particular substrates, which in turn do their own particular things appropriate to the phase. Somewhat Ironically, the connections between the Cyclins and the activities of each phase aren't accurately known. Most simply it is just known that at each particular time there is more or less of some particular cyclin present, and at that time, or shortly after that time, or whatever, various specific things happen.

I'll use the next post to go through exactly what happens around the M phase.



I stumbled across this URL, which appears to be a set of lecture slides on this topic.
http://io.uwinnipeg.ca/~simmons/mitosis/sld001.htm

 

[Another God]

From what I can figure out from my lecture notes and Alberts, the connections between the increase in M-Cyclin activation, and the consequential occurrings of M Phase aren't well understood. So, like all that I have read, I will fudge over exactly how M-Cyclin (CDK1-A and B) causes this stuff to happen, and just jump straight into what happens...

Firstly, I should point out that as the concentration of M-cyclin increases throughout G₂ it is actually inactivated. It is held in this inactivated state by phosphorylation by Wee1. This allows this Cyclin levels to build up some event causes Polo Kinase activate Cdc25, which in turn removes the phosphorylation on the M-cyclin. The activated M Cyclin then activates more cdc25 while inhibiting action of Wee1, causing an exponential release of M-Cyclin from is phosphorylated bondage.

So, this method of action means that a gradual growth in M-Cyclin concentration doesn't cause a gradual entry into Mitosis, but instead waits until the right moment, and then commits everything to the Mitotic process.

A consequence of this activation is also that Cdc25 activates the 'Anaphase Promoting Complex" (APC). This enzyme, once activated begins Ubiquitinating enzymes with the appropriate recognition sites: Included in that description are Securin and M-Cyclin.

Securin is a protein which inhibits 'Separase'. Separase is the molecule which acts on the proteins which hold the Sister chromatids together. By degrading Securin, Separase is able to act, and the sister chromatids are released, able to be pulled apart.

M-Cyclin is also targeted for degradation by APC too though, which does make a lot of sense. It built up, it was suddenly activated, it switched on all of the events which need to take place for mitosis to occur, and now it is no longer needed. It is, as a direct consequence of its actions, destroyed.



I don't know if anyone else out there is bothering to read this, and if you have got this far, I don't know how much of it is over your head and just a bunch of Jargon (I understand it if it is...there are so many protein names and technical molec. bio terms thrown around in this field...) but even if so, I think this stuf is really damn interesting. It's incredible finally being able to understand how stuff like this works...