Amino acids in the central region of wild-type p53 form direct DNA contacts and conformationally coordinate the protein for stable sequence-specific interactions at p53 response elements; the hotspot cancer amino acid mutations in Arg 248 (R248) and Arg 273 (R273) correspond to amino acid residues that make direct contact with the DNA backbone (Cho et al., 1994). Here, TP53 is linked to cancer.