Regulation of the Cell Cycle at Internal Checkpoints

Regulation at Internal Checkpoints

It is essential that the daughter cells are 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 an abnormal cell. To prevent a compromised cell from continuing to divide, internal control mechanisms operate at three main cell cycle checkpoints. A checkpoint is one of several points in the eukaryotic cell cycle at which the progression of a cell to the next stage in the cycle can be halted until conditions are favorable (e.g. the DNA is repaired). These checkpoints occur near the end of G₁, at the G₂/M transition, and during metaphase .

Internal Checkpoints During the Cell Cycle

The cell cycle is controlled at three checkpoints. The integrity of the DNA is assessed at the G1 checkpoint. Proper chromosome duplication is assessed at the G2 checkpoint. Attachment of each kinetochore to a spindle fiber is assessed at the M checkpoint.

The G₁ Checkpoint

The G₁ checkpoint determines whether all conditions are favorable for cell division to proceed. The G₁ checkpoint, also called the restriction point (in yeast), is a point at which the cell irreversibly commits to the cell division process. External influences, such as growth factors, play a large role in carrying the cell past the G₁ checkpoint. The cell will only pass the checkpoint if it is an appropriate size and has adequate energy reserves. At this point, the cell also checks for DNA damage. A cell that does not meet all the requirements will not progress to the S phase. The cell can halt the cycle and attempt to remedy the problematic condition, or the cell can advance into G₀ (inactive) phase and await further signals when conditions improve.

If a cell meets the requirements for the G₁ checkpoint, the cell will enter S phase and begin DNA replication. This transition, as with all of the major checkpoint transitions in the cell cycle, is signaled by cyclins and cyclin dependent kinases (CDKs). Cyclins are cell-signaling molecules that regulate the cell cycle.

The G₂ Checkpoint

The G₂ checkpoint bars entry into the mitotic phase if certain conditions are not met. As with the G₁ checkpoint, cell size and protein reserves are assessed. However, the most important role of the G₂ checkpoint is to ensure that all of the chromosomes have been accurately replicated without mistakes or damage. If the checkpoint mechanisms detect problems with the DNA, the cell cycle is halted and the cell attempts to either complete DNA replication or repair the damaged DNA. If the DNA has been correctly replicated, cyclin dependent kinases (CDKs) signal the beginning of mitotic cell division.

The M Checkpoint

The M checkpoint occurs near the end of the metaphase stage of mitosis. The M checkpoint is also known as the spindle checkpoint because it determines whether all the sister chromatids are correctly attached to the spindle microtubules. Because the separation of the sister chromatids during anaphase is an irreversible step, the cycle will not proceed until the kinetochores of each pair of sister chromatids are firmly anchored to at least two spindle fibers arising from opposite poles of the cell.