Tumor protein p53-cisplatin-modified DNA complex (p53-Pt-DNA complex)

The p53-cisplatin-damaged DNA complex is a molecular assembly formed when the tumor suppressor protein p53 binds to genomic DNA containing platinum-induced lesions. Cisplatin, a widely used chemotherapeutic agent, exerts its cytotoxic effects by forming covalent intrastrand and interstrand crosslinks, primarily at guanine residues (Dasari & Bernard Tchounwou, 2014). The binding of p53 to these damaged sites is a critical step in the cellular DNA damage response, as p53 acts as a guardian of the genome to determine cell fate (Levine, 1997). Upon binding to cisplatin-modified DNA, p53 can facilitate the recruitment of DNA repair machinery or, if the damage is irreparable, initiate programmed cell death (apoptosis) through the transactivation of pro-apoptotic genes like BAX and PUMA (Subramanian et al., 2000). The integrity of this complex is vital for the efficacy of platinum-based therapies, and mutations in the TP53 gene often disrupt this interaction, leading to chemoresistance in various cancers (Turchi et al., 2000). This complex serves as a focal point for understanding how cells sense and respond to platinum-induced genotoxicity, and therapeutic strategies often aim to stabilize this interaction or restore p53 function to enhance the sensitivity of tumor cells to cisplatin.

Other names

p53-cisplatin DNA adduct complexp53-Pt-DNAp53 binding to cisplatin-damaged DNAp53-cisplatin-DNA complex

Cisplatin induces DNA crosslinks which are recognized and bound by p53, leading to the activation of apoptotic pathways or cell cycle arrest (Dasari & Bernard Tchounwou, 2014; Subramanian et al., 2000).