August 7, 2025

Aashna Chavan

DuPont Manual High School

12th Grade

The cell cycle is an intensely regulated series of events that enable cells to grow, replicate, and divide. The cycle is essential for organismal growth, tissue repair, and development. The cycle contains four distinct phases—G1 (Gap 1), S (Synthesis), G2 (Gap 2), and M (Mitosis)— each specializing in specific cellular activities. Embedded in this cycle are regulatory mechanisms called checkpoints that act as surveillance to ensure accurate progression through the cell’s life cycle. Disruptions during checkpoints can lead to uncontrolled cell proliferation and the development of cancer.

Cancer is the result of uncontrolled cell growth, which is caused by mutations in genes that regulate the cell cycle. Normally, the cell cycle is tightly regulated at each checkpoint by tumor-suppressing proteins. These proteins ensure that cells only divide when conditions are safe and the DNA is undamaged. However, when mutations occur in these regulatory genes, damaged cells may bypass the checkpoints and continue dividing despite having errors in their DNA. Over time, these abnormal divisions lead to an increased presence of mutated cells, promoting unchecked growth, invasion of tissue, and eventually, tumor formation. Because of this, proper regulation of the cell cycle is crucial for preventing cells from becoming cancerous.

The G1 phase is the first portion of the cell cycle, where cells grow, produce RNA, and make the proteins needed for DNA replication. At the end of this phase lies the G1/S checkpoint, also called the restriction point. During this checkpoint, the cell checks itself to ensure it has the proper cell size and abundance of nutrients, and to see if there is any present DNA damage. If damage or increased cell stress is detected, the protein p53 is activated. Activated p53 proteins bind to the promoter region of the CDKN1A gene and upregulate its transcription. This leads to increased production of the Waf1 protein, which binds to and inhibits cyclin-CDK complexes. In doing so, Waf1 prevents these complexes from phosphorylating the retinoblastoma protein (Rb). When Rb remains unphosphorylated, it stays bound to the E2F transcription factors, therefore blocking the transcription of genes required for DNA synthesis. This inhibition effectively halts the cell cycle at the G1/S checkpoint, giving the cell time to repair itself before heading into the S phase. If the DNA damage is too severe and cannot be repaired, p53 may instead activate pro-apoptotic genes, leading to programmed cell death through apoptosis to prevent the proliferation of damaged cells.

Besides these phases, cells enter a resting state called the G0 phase, where cells exit the cell cycle and no longer divide. Cells in G0 can be triggered to re-enter the cycle by growth factors. However, if they're forced to divide again with accumulated mutations, it can lead to abnormal growth. Some cancer cells avoid G0 completely, keeping themselves in a constant state of division, especially when oncogenes like MYC are activated.