How does a cell know when to stop dividing?
A cell stops dividing through built-in checkpoints that detect DNA damage, energy deficit or other stress signals. How those brakes work and how pathogens hijack them is well understood, although translating this into therapies is still in its early stages.
The cell has built-in checkpoints in its division cycle. The most important one sits at the transition from the preparation phase to the DNA-copying phase. At that moment, a network of proteins decides whether the cell may proceed. A protein called Rb acts as a brake: as long as that brake is engaged, the cell does not divide. Special 'motor-protein pairs' (cyclins and their partners) must release that brake. If something is wrong, another protein, p53, steps in: it activates its helper p21, which blocks the motors and keeps the brake locked.
An alarm can also go off during the actual copying of DNA. If the mechanism that unwinds the DNA helix becomes uncoupled from the mechanism that makes the copy, the cell sends out an emergency signal. All copying sites in the cell then stop simultaneously. This prevents half-copied or damaged genetic material from being passed on to daughter cells.
If the cell fails to repair the damage, the halt can become permanent. This is called cellular senescence: the cell continues to live but never divides again. This state is a fundamental ageing mechanism that contributes in the long term to cancer, atherosclerosis and joint disease. In kidney damage, the temporary halt actually serves a protective function: it gives the cell the opportunity to recover. Two proteins that then appear in the urine can signal that halt early, before classic symptoms of kidney damage occur.
Pathogens exploit the same system. Cytomegalovirus (a herpesvirus) locks the cell in place while simultaneously switching on the copying genes, creating an ideal environment for the virus. The bacterium that causes Legionnaires' disease attaches a chemical label to ribosomes, the cell's protein factories, via an injected protein, after which protein synthesis falters and division stops. The virus and the bacterium do not do this to protect the cell, but to better replicate themselves.
Researchers are also trying to deploy this system in a targeted way. The antimalarial drug artesunate inhibits the accelerator of the cell cycle via an antioxidant signal in cell culture and animal research, which may counteract fibrosis in the eye. Whether this works in humans has not yet been investigated. Another laboratory tool makes an existing chemotherapy drug light-sensitive, so that cell division can be stopped at an exact moment with a pulse of light. This is, for now, a research tool, not a treatment.
All claims are based on the supplied PMIDs (28729727, 34903047, 39374399, 26044835, 41468429, 39151383, 33035402). The mechanistic basis of the cell-cycle checkpoints is robustly demonstrated across multiple sources; the viral and bacterial interventions are strongly and moderately supported, respectively. Artesunate and the light-activated technique have been demonstrated exclusively in cell and animal research.