p53 Gene: The Crucial Guardian Against Cancer
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Cancer biologists have long hoped to discover a single step that determines whether cells become cancerous. By targeting drugs at that step, physicians would be able to stop a cell from becoming cancerous just as a switchman stops a train from going down the wrong track. It turns out that a gene called p53 may be that switch. p53 acts as the cell"s director of damage control. A healthy cell keeps a small number of p53 proteins around, continuously degrading them and replenishing the supply. But if carcinogens damage a cell"s DNA and sets it on the path to cancer, the cell switches into high alert. If everything is working right, something signals the p53 to stop degrading and tells it that it is time to be active. The p53 supply builds up, p53 starts acting like an office clerk who, discovering a typo in an original document that is about to be copied, turns off the copier until he can fix the typo. p53 turns off the cell"s copying machinery and stops the progression of cell cycle until the cell can repair its damaged DNA. p53 floats toward the cell"s genes and slips into a specific stretch of DNA triggering expression of genes which make proteins that directly inhibit growth of the cell. The tumour-to-be is stopped dead. p53 also activates the transcription of proteins involved in DNA repair. Sometimes p53 acts more like a clerk so disgusted with the many typos that he just trashes the document: p53 activates the cell"s suicide software, resulting in apoptosis (programmed cell death).
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Except when it doesn"t. Even good genes can go bad, and most often, the p53 gene goes bad by undergoing a mutation, typically a spelling mistake. One of the 2362 chemical "letters" (designated A, T, G and C) that make up the p53 gene changes into another letter. The p53 protein that the gene makes is garbled too. And proteins are not very forgiving of errors. A single wrong letter in a crucial part of the p53 gene produces a protein with a wrong molecule; the protein is now not able to suppress tumours.
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The Li-Fraumeni families inherit their p53 mutations. If the sperm or egg from which a baby grew held a mutant p53, then every single cell in her body will also harbour a mutant copy. In theory, inheriting only one mutant p53 gene, from one parent, should not be a problem as long as the child inherits a healthy p53 gene from the other parent. The healthy copy should make enough p53 to keep tumours at bay. But p53 doesn"t work that way.
First of all, each cell with one bad p53 gene is only one mutation away from completely lacking the function of this critical gene. That mutation can occur when the cell makes a spelling mistake as it copies its gene before dividing into two cells. Then the cell has lost its primary defense against cancer. A single mutant gene is enough to leave a cell with no healthy tumour-quashing p53. And just one out-of-control cell can give rise to deadly tumour.
