9.7Checkpoint Mechanism of the Cell Cycle
Cells grow through repetition of the cell cycle. One of the most important points in cell growth is that genetic information (the genome) is accurately replicated and distributed to the two resulting cells. To make sure that these processes take place without fail, checkpoints located at each phase of the cell cycle verify whether the cell is ready to progress to the next phase.
The G1 checkpoint determines whether the cell should initiate DNA synthesis. DNA is routinely damaged in various ways; if DNA synthesis is initiated before the damage is repaired, correct replication does not take place, likely resulting in mutation or cell death. Cells therefore have a mechanism that checks whether the DNA sequence or structure is correct, and when errors (or damage) are detected, p53 is activated by acetylation or phosphorylation, and the activated p53 in turn activates (or suppresses, depending on the gene) many genes.
One of the roles of p53 is to activate the gene encoding p21 (a CKI) to produce many molecules of p21, thereby suppressing the action of the G1 cyclin and the G1 CDK. As a result, the cell does not progress into the S phase, and DNA damage is repaired during this delay time. Once the repair is complete, p53 is inactivated and p21 is degraded, allowing the cell to progress into the S phase. If the DNA damage is too severe to be repaired, p53, after being modified, activates the gene that induces apoptosis (discussed later), leading to the death of the cell.
To prevent defective DNA from being distributed to the daughter cells, the G2 checkpoint suppresses the activity of the G2 cyclin-CDK complex (thus keeping the cell from entering the M phase) until it confirms that the DNA is not damaged and its synthesis is complete.
To ensure that the genome is accurately distributed to the two daughter cells, the M checkpoint keeps the cell from progressing to the next phase until microtubules (see Fig. 6-5 in Chapter 6) correctly bind to all chromosomes. These “check and go” systems are located at key points of the cell cycle, making sure that the genome is distributed to the two daughter cells without fail. In terms of the growth regulation mechanism for the somatic cells of eukaryotic multicellular animals (particularly that of mammals), a condition in which the uncontrolled growth of cells is suppressed is set as the default, and a positive growth regulation mechanism is temporarily activated to initiate the cell cycle only when cell growth is necessary. However, even then, a mechanism is at work to ensure that the genome is accurately replicated and distributed to daughter cells through careful operation of the “check and go” system. In unicellular organisms, on the other hand, a mechanism is in place to increase the number of individuals (cells) as much as the living environment will permit.