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The tumor suppressor protein p53 regulates the expression of many genes involved in DNA repair, cell cycle arrest, and apoptotic cell death. Mutations that inactivate p53 are found in over 50% of human cancers, and most of the cancer-associated mutations are within its DNA-binding domain. The image shows a tetramer of the p53 DNA-binding domain complexed with DNA (Protein Data Bank entry 2ac0). The tetramer subunits are shown as light blue, green, orange, and yellow ribbons, with red spheres marking several major "hot spots" of mutation. The DNA is shown in purple and blue with simplified sugars and bases. References:
Structural basis of restoring sequence-specific DNA binding and transactivation to mutant p53 by suppressor mutations. Suad O, Rozenberg H, Brosh R, Diskin-Posner Y, Kessler N, Shimon LJ, Frolow F, Liran A, Rotter V, Shakked Z. J Mol Biol. 2009 Jan 9;385(1):249-65.
Structural basis of DNA recognition by p53 tetramers. Kitayner M, Rozenberg H, Kessler N, Rabinovich D, Shaulov L, Haran TE, Shakked Z. Mol Cell. 2006 Jun 23;22(6):741-53.
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