The cell cycle is the fundamental process by which cells grow and divide, forming two daughter cells from a single parent cell. This organized series of events is necessary for the growth, development, and repair of tissues within an organism. It ensures new cells are available to replace old or damaged ones, supporting overall body health.
The Cell Cycle Explained
The eukaryotic cell cycle is divided into four phases: G1, S, G2, and M. G1, S, and G2 are collectively known as interphase. During the G1 phase, or “first gap,” the cell grows, increases its proteins, and duplicates organelles like mitochondria and ribosomes. This prepares the cell for DNA replication.
Following G1, the cell enters the S phase, where DNA replication occurs. Each chromosome in the cell’s nucleus is duplicated, forming two identical sister chromatids. Once DNA synthesis is complete, the cell moves into the G2 phase, or “second gap.” Here, it continues to grow and synthesizes proteins necessary for chromosome manipulation and division.
The final phase is the M phase, which encompasses mitosis and cytokinesis. Mitosis is where the cell’s nucleus divides, separating replicated chromosomes into two new nuclei. Cytokinesis then follows, dividing the cell’s cytoplasm and cell membrane to form two daughter cells. These new cells can then enter their own G1 phase or a resting state called G0 if they temporarily or permanently stop dividing.
Regulating Cell Division
The progression of cells through the cell cycle is controlled by internal mechanisms known as checkpoints. These checkpoints ensure the cell only advances to the next phase when preceding events are complete and conditions are suitable for division. For example, a checkpoint at the end of G1 ensures the cell is ready for DNA synthesis, while another at the start of G2 verifies that DNA replication is complete and the cell is prepared for mitosis.
Specialized proteins regulate these checkpoints and the cell cycle. Some are encoded by proto-oncogenes, which normally promote cell growth and division. When mutated, proto-oncogenes become oncogenes, increasing cell cycle progression. Other regulatory proteins are produced by tumor suppressor genes, which act as negative regulators, halting the cell cycle until issues, such as damaged DNA, are resolved.
These regulatory proteins, including those involved in DNA repair, ensure genomic integrity. If DNA damage is detected, the cell cycle can be temporarily halted, allowing for repair mechanisms to activate. If the damage is too extensive to be repaired, these control mechanisms can initiate programmed cell death, a process called apoptosis, to eliminate the potentially harmful cell.
When Cell Cycle Control Fails
Cancer arises when cell cycle control mechanisms break down, leading to unchecked cell division. This disruption often begins with mutations within the genes that code for regulatory proteins and checkpoint components. When these genes are altered, the resulting proteins may be malformed or non-functional, causing the cell cycle to operate without proper oversight.
For instance, a mutated proto-oncogene can become an oncogene, continuously promoting cell division even in the absence of normal growth signals. Conversely, if a tumor suppressor gene mutates, its ability to halt the cell cycle or trigger apoptosis in response to DNA damage is compromised.
Cancer cells exhibit several characteristics due to this dysregulation. They can bypass cell cycle checkpoints, replicate even with damaged DNA, and may not require external growth factors to divide. Cancer cells often evade programmed cell death, allowing them to survive and proliferate despite accumulating abnormalities, eventually leading to tumor formation.
Therapeutic Strategies Targeting the Cell Cycle
Understanding the cell cycle’s role in uncontrolled cell division has influenced the development of cancer treatments. Many therapeutic strategies aim to disrupt the rapid proliferation characteristic of cancer cells or to restore normal cell cycle control.
Chemotherapy, a traditional cancer treatment, targets rapidly dividing cells. These drugs induce DNA damage, preventing cancer cells from synthesizing new DNA or disrupting their ability to complete mitosis. For example, alkylating agents add groups to DNA, hindering replication, while mitotic inhibitors like paclitaxel disrupt the formation of structures needed for cell division.
Newer therapies, known as targeted therapies, focus on specific molecular components of the cell cycle that are often dysregulated in cancer cells. Cyclin-dependent kinase (CDK) inhibitors, such as palbociclib, ribociclib, and abemaciclib, are examples. These inhibitors block the activity of CDKs, which are proteins that drive cell cycle progression, halting the division of cancer cells, particularly in the G1 phase.