Regulation Of Cell Cycle

Fig 2.1

To regulate the cell cycle, there are checkpoints which occur at different intervals. These checkpoints evaluate if a cell should or shouldn't proceed to the next phase based on cues which are both external and internal.

These checkpoints occur at (i)-the end of G1 phase, (ii)-the end of G2 phase, and (iii)-the M phase more particularly at metaphase.

Fig 2.2

The first checkpoint checks the cells DNA before replication if the cell is growing as it should and if it has the necessary resources or nutrients to divide.

The second checkpoint checks if the DNA has replicated correctly and if it has enough resources to further continue.

The third checkpoint checks if chromosomes have aligned as they should have at the equator of the cell and if the spindle is attached to the centromere.

These cues trigger signalling pathways inside the cell that activate, or inactivate, a set of core proteins that move the cell cycle forward. These core proteins are the cyclins, CDK's and tumour suppressors.

Fig 2.3

Cyclins are a group of related proteins, and there are four basic types found in humans and most other eukaryotes: cyclin D, cyclin E, cyclin A and cyclin B. The level of each Cyclin varies throughout the cell cycle as the cell passes from one phase to the other. For instance, cyclin B promotes the events of M phase, such as nuclear envelope breakdown and chromosome condensation. The level of each cyclin remains low for most of the cycle except when it is needed. For example, The cyclin B peaks dramatically when the cell moves from G2 to M.

Fig 2.4

These cyclins bind with an enzyme called CDK(Cyclin-Dependent Kinase) thus, making the enzyme active. This complex leads to a cascade of phosphorylation of several different proteins making the proteins more or less active. These target proteins are the ones appropriate to the cell cycle period. Unlike, cyclins the level of CDK's remain constant throughout.

Fig 2.5

Negative cues such as DNA damage decrease or block the activity of CDK's and cyclins. For the cell, to be able to deal with this damage, it releases a protein called p53, a famous tumour suppressor often described as “the guardian of the genome.”

It works at different levels to prevent the cell with damaged DNA to divide. At the G1 checkpoint, it triggers the production of CDK inhibitor proteins which bind to CDK-cyclin complex to block its activity. So, the cell cannot proceed to the next phase. Then, tries to repair the DNA by activating DNA repair enzymes. If the DNA is beyond repair the cell destroys itself and this process is known as apoptosis.

References

1)GEMS-GMU-Future Scientists of UAE program.

2) https://www.khanacademy.org/science/biology/cellular-molecular-biology/stem-cells-and-cancer/a/cell-cycle-checkpoints-article

3) https://www.youtube.com/watch?v=M1BF2KWsKwE

4) https://www.sciencedirect.com/topics/medicine-and-dentistry/cell-cycle-checkpoint

5) https://www.youtube.com/watch?v=1mo80kTZgW4