36 Control of the Cell Cycle
It is essential that daughter cells be exact duplicates of the parent cell. Mistakes in the duplication or distribution of the chromosomes lead to mutations that may be passed forward to every new cell produced from the abnormal cell. To prevent a compromised cell from continuing to divide, there are internal control mechanisms that operate at three main cell cycle checkpoints at which the cell cycle can be stopped until conditions are favorable (Figure 1).
The first checkpoint (G1) determines whether all conditions are favorable for cell division to proceed. This checkpoint is the point at which the cell irreversibly commits to the cell-division process. In addition to adequate reserves and cell size, there is a check for damage to the genomic DNA. A cell that does not meet all the requirements will not be released into the S phase.
The second checkpoint (G2) bars the entry to the mitotic phase if certain conditions are not met. The most important role of this checkpoint is to ensure that all of the chromosomes have been replicated and that the replicated DNA is not damaged.
The final checkpoint (M) occurs in the middle of mitosis. This checkpoint determines if all of the copied chromosomes are arranged appropriately to be separated to opposite sides of the cell. If this doesn’t happen correctly, incorrect numbers of chromosomes can be partitioned into each of the daughter cells, which would likely cause them to die.
Regulator Molecules of the Cell Cycle
In addition to the internally controlled checkpoints, there are two groups of intracellular molecules that regulate the cell cycle. These regulatory molecules either promote progress of the cell to the next phase (positive regulation) or halt the cycle (negative regulation) (Figure 2). Regulator molecules may act individually, or they can influence the activity or production of other regulatory proteins. Therefore, it is possible that the failure of a single regulator may have almost no effect on the cell cycle, especially if more than one mechanism controls the same event. It is also possible that the effect of a deficient or non-functioning regulator can be wide-ranging and possibly fatal to the cell if multiple processes are affected.
Positive Regulation of the Cell Cycle
Two groups of proteins, called cyclins and cyclin-dependent kinases (CDKs), are responsible for the progress of the cell through the various checkpoints (Figure 3). The levels of the four cyclin proteins fluctuate throughout the cell cycle in a predictable pattern. Increases in the concentration of cyclin proteins are triggered by both external and internal signals. After the cell moves to the next stage of the cell cycle, the cyclins that were active in the previous stage are degraded.
Cyclins are active only when they are tightly bound to CDKs. When a cyclin is tightly bound to its CDK, it will phosphorylate other proteins (add a phosphate chemical group), which activates the protein by changin