TP53 and Li-Fraumeni syndrome: In Li-Fraumeni syndrome (a condition where patients present with germline p53 mutations and have a predisposition to early-life cancer development), point mutations within the OD (R337C, A347D, or L344P) destabilize tetramer formation and decrease the ability of p53 to bind DNA, as well as activate transcription of p21, Bax, and PUMA (Jeffrey et al., 1995; Davison et al., 1998; Lomax et al., 1998).