34.3:
The Cell Cycle Control System
The cell cycle involves the duplication of the intracellular content, followed by the division into two daughter cells.
Replication of cellular content, especially the DNA, is highly critical, and any mistake during the process can lead to conditions such as cancer.
So how do cells prevent any errors during division?
The cell cycle control system features regulator proteins that halt the cycle at various checkpoints.
At every checkpoint, the regulator proteins prevent the initiation of each step until the earlier stages are completed and any errors have been corrected.
Generally, the control system has three crucial checkpoints found in the G1, G2, and M phases.
At the G1 checkpoint, the regulator protein checks if the cell has reached the critical size and the DNA is free from errors. It also checks whether enough nutrients and growth factors are present to begin DNA synthesis.
At this point, if the cell does not receive the necessary signal, it switches to a resting state called the G0 phase until all the conditions are met.
The cells that pass the G1 checkpoint transit through the synthesis, or S-phase, when the DNA gets replicated.
After this, the cell encounters a second checkpoint at the G2 phase, where the regulator proteins check any errors in the DNA and whether the cell has an appropriate size to enter Mitosis or M-phase.
During Mitosis, the control system verifies if the chromosomes are attached to the spindle and are accurately aligned so that the cycle proceeds for cell division. If at any point the regulator protein detects irreparable damage, cell death occurs. One type of critical regulator proteins are the cyclin-dependent protein kinases, or CDK. CDKs form complexes with cyclins, and their activity affects proteins directly involved in cell growth and DNA synthesis.
34.3:
The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell division in the absence of a control mechanism leads to cancer and many genetic diseases.
To ensure DNA replication occurs correctly and each daughter cell inherits the right number of chromosomes, the cell has surveillance mechanisms that make up the cell cycle control system. There are at least two known cell cycle control methods. One of these processes includes a cascade of protein phosphorylations that transitions a cell from one phase to the next. Also, there is a series of checkpoints that monitor the completion of essential events and, if necessary, delay progression to the next phase. At every checkpoint, the regulator proteins prevent the cell initiation from entering the next phase until the previous phase's errors are rectified.
The first form of regulation includes a highly regulated family of kinases. Kinase activation requires interaction with a second subunit expressed at fixed points of the cell cycle. This secondary component is termed as- a phase-specific "cyclin" that combines with its partner "cyclin-dependent kinase" (CDK), forming an active complex, each of which exhibits distinct substrate specificity. Regulatory phosphorylation and dephosphorylation fine-tune the function of cyclin-CDK complexes, ensuring a well-defined progression.
The second form of cell cycle regulation – checkpoint control, is more of a surveillance mechanism. Cell cycle checkpoints identify defects in crucial events such as DNA replication and chromosome segregation. For instance, DNA damage triggers a signaling cascade that activates several cell cycle inhibitors. These inhibitors bind critical cell cycle proteins to arrest the cycle until the risk of mutation has been eliminated.
Suggested Reading
- Golias, C. H., A. Charalabopoulos, and K. Charalabopoulos. "Cell proliferation and cell cycle control: a mini-review." International journal of clinical practice 58, no. 12 (2004): 1134-1141.
- Johnson, D. G., and C. L. Walker. "Cyclins and cell cycle checkpoints." Annual review of pharmacology and toxicology 39 (1999).