p53 is one of the most important genes in current research into a cure for cancer. It is a 53 kilodalton protein product (hence the name) encoded on the short arm of chromosome 17. It is one of the primary proteins responsible for apoptosis (programmed cell death), and responses in dealing with DNA damage. Ordinarily, when a cell is damaged, by radiation or chemicals, p53 becomes active, and prevents cell division. If the cell is too damaged for DNA repair pathways to mend, it causes the cell to undergo apoptosis. It is the single most common gene mutation present in cancer. When a cell loses p53, through mutation generally, it rapidly accumulates other mutations, which can either kill the cell, or eventually make it cancerous. Most of the cancer tumors that respond well to radiation and chemotherapy do not have the p53 mutation. Therefore, when they are damaged by radiation, p53 stops their replication and causes them to apoptose, killing the tumor. This does not happen in tumors lacking p53, so it makes p53 a very appealing target for gene therapy to insert into cancer cells, making them vulnerable to radiation treatment again.

There is also a genetic disease involving p53 mutation. Because humans have 2 copies of this gene, sometimes a person will inherit a defective copy from one parent, and a normal copy from the other parent. This means that a mutation in the single normal gene results in total loss of p53 in that cell. These individuals have a very high rate of cancer, generally with a very poor prognosis for recovery.

The role of p53 in sunburn.

To help understand the function of p53, described above by CrazyIvan, it is useful to employ an example.

UV radiation is a powerful carcinogen, and when our skin is exposed to this radiation, the DNA in the skin cells is damaged at random points.
As CrazyIvan has explained, when DNA is damaged, the p53 gene is upregulated. This causes the cell to undergo programmed cell death, otherwise known as apoptosis.
When many skin cells are damaged through exposure to UV radiation, this mass apoptosis is manifested as layers of dead skin that you can peel off in nice large chunks. (see the art of peeling large pieces of skin delicately)

Consider the fact that you have 2 copies of the p53 gene in each cell, which is represented as p53+/+. Now, suppose one copy of p53 is damaged in some of the cells (p53+/-). The next time you go and get sunburnt, the apoptosis of the p53+/- cells is less efficient, but usually still goes ahead. However, if you damage the DNA of a p53+/-cell, and it happens to knock out the second copy of p53 in one or more of your skin cells, things can start to get very dangerous.

p53-/- cells do not undergo apoptosis. This does not mean it is now a cancerous cell, but rather a cell without emergency brakes. p53-/- cells are genetically unstable and are more prone to tumours. If you were to get sunburnt a third time, and damage the DNA in a p53-/- cell, the cell would be unable to self destruct. If this mutation activates an oncogene, the result is a cancerous cell.

Because of the way p53 functions, it is often referred to as a tumour suppressor gene, or the “guardian of the genome”.

Now you should have a fair idea of how to quickly and efficiently induce basal cell carcinomas.

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