The p53 gene engaged in DNA repair

The p53 gene is classified as a tumor suppressor gene, and is nicknamed “the guardian of the genome” because it will activate apoptosis if there is any DNA damage. If a mutation in the p53 gene causes impaired function or loss of function, other mutations can build up quickly, and a cancer will develop rapidly.

A point mutation replacing one nucleotide for another, will likely code for a different amino acid, altering the protein’s primary structure (its amino acid sequence). However, a point mutation sometimes codes for the same amino acid. Suppose an arginine from the DNA binding domain (DBD) is altered to a serine. Its secondary structure might have a severely altered DBD, stopping it from binding to and scanning nucleotide sequences. Sometimes a different amino acid is still in the amino acid same group, and so the higher levels of structure are not drastically affected. Without this function the protein is effectively useless. Its tertiary structure, the three dimensional shape of the entire protein, may be severely disrupted, perhaps becoming more elliptical than globular, or perhaps a section becomes more unwound and diffuse. The quaternary structure of the protein (how it interacts with other subunits) might be entirely non-functional, meaning that the protein might not fit where it needs to, or to act correctly once attached to another subunit. It may also attach or react where it should not.

Cells normally require p53 during checkpoints, before continuing on to cell division. Without the ability to check for DNA damage and to activate apoptosis in the event of DNA damage, irregular cells can proliferate uncontrollably. In effect, a dysfunction in p53 helps to induce “cell immortality”, and it causes genetic instability (increasing the number of mutations allowed into the DNA). As more mutations interfere with restriction points and the cell cycle, the process snowballs into a complex tumor. Cells which become anchor-independent, that do not have to be attached to a cytoskeletal component, can begin tissue invasion and metastasis (movement to other locations through the bloodstream).

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