A majority (∼90%) of cancer-associated p53 mutations occur within the DBD, where they cluster into discernible “hotspots”9,10, resulting in the protein’s inactivation through alterations in residues that are crucial for either DNA interactions (contact mutants) or proper folding (structural mutants), although it is now apparent that some mutations (such as R248W) possess both characteristics6. The gene discussed is TP53; the disease is cancer.