Cell Cycle Checkpoints and the Role of Apoptosis

Cell Cycle Checkpoints and Regulation

Several checkpoints coordinate and regulate the transition from one stage of the cell cycle to the next. These include:

The G1 to S Phase Transition

The checkpoint situated at the end of the G1 stage was first described in the yeast Saccharomyces cerevisiae and was designated as START or the restriction point. Once this point is passed, the S phase inevitably occurs, and the cell cycle continues, eventually ending with cell division. Overcoming this point depends on cell size and the presence of extracellular growth factors. Thus, in the presence of these factors, cells pass through and continue their cell cycle into the S phase. If growth factors are absent during the G1 phase, the cell enters a period of quiescence called G0, where it can remain for a variable amount of time or even for the rest of its life.

The G1 checkpoint also serves as a measure to prevent cell cycle progression if errors are detected in the DNA, as the cell is not permitted to pass to the S phase until they have been repaired.

The G2 to M Phase Transition

The step from G2 to M is a regulatory point that is less common and is characteristic of oocytes, which can remain in G2 for long periods until they are hormonally stimulated to enter the M phase. The G2 checkpoint also serves to prevent the initiation of mitosis if the DNA is damaged or has not been replicated successfully. Arrest in G2 allows time for the correction of errors or DNA damage.

The M Phase Checkpoint

The M checkpoint stops mitosis if the mitotic spindle is not well-formed or if chromosomes are not properly aligned upon it.

Apoptosis: Programmed Cell Death

Cells are not immortal; after a certain number of cell cycles, programmed cell death or apoptosis occurs. It is a physiological mechanism of normal cell death that is genetically regulated and essential for the maintenance of adult tissues and embryonic development.

Functions of Apoptosis in Organisms

Thanks to apoptosis, the number of cells in adult organisms is balanced within tissues that perform continuous cell turnover. This process eliminates altered and potentially dangerous cells, such as those infected by viruses, those with DNA lesions, or those carrying cancerous mutations.

During embryonic development, programmed cell death also plays a key role by eliminating unnecessary cells. Examples include:

• Larval tissues: These are no longer needed after the metamorphosis of insects and amphibians.
• Interdigital tissue: Observed in the first stages of the formation of the fingers and toes.
• Neurons: Those that have not properly formed their synapses during the development of neural tissue.

The Biological Process of Apoptosis

In the process of apoptosis, chromosomal DNA is cleaved at the linker regions between nucleosomes. The resulting pieces of chromatin condense, and the nucleus disintegrates into small fragments. Finally, the cell shrinks and breaks down into membrane-bound fragments called apoptotic bodies.

This process involves a family of proteases known as caspases (cysteinyl aspartate proteases). Malfunctions in the processes mediated by these enzymes are primary factors in the development of tumors and autoimmune diseases.