Tumor suppressors are genes that result in tumor formation after suffering a mutation that destroys their normal function. p53 (a protein of 53 kilodaltons) is an important tumor suppressor gene.
Loss of p53 function leads to tumorigenesis, and a large fraction of human tumors examined display p53 gene mutations. Although its biochemical actions are not yet clear, p53 is a DNA-binding protein that plays a role in regulating the cell cycle, preventing inappropriate movement of G1 cells into S phase. Loss of such a checkpoint could lead to the loss of cell growth control assoicated with cancer.
Binding to specific DNA sequences is essential for the proper functioning of p53. This was revealed in 1994 when the structure of the DNA-binding domain in contact with an oligonucleotide containing the binding sequence was determined by x-ray crystallography. Of great interest is that the amino acid residues in closest contact with DNA are those that have been shown most often to be changed in p53 mutant genes isolated from human tumors.
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