DNA cross-linking via platinum adducts

DNA cross-linking via platinum adducts describes a process where platinum-based anti-cancer drugs (notably cisplatin, carboplatin, and oxaliplatin) form covalent bonds with DNA, mostly at the N7 position of purine bases. This interaction primarily induces intra- and interstrand DNA cross-links as well as DNA-protein cross-links, causing structural distortion of the DNA helix. Such lesions block DNA replication and transcription, ultimately causing cell cycle arrest and apoptosis. The effectiveness of these agents is influenced by cellular DNA repair capacities, especially those related to nucleotide excision repair. While this mechanism underlies the efficacy of platinum-based chemotherapy—one of the mainstays of treatment for a variety of solid tumors—it is also associated with significant toxicities and frequent issues with resistance in tumors[2][3][4][5][7].

Other names

DNA-protein cross-linksDNA-platinum adductsplatinum-DNA adductsPt-DNA cross-linking

Formation of covalent platinum adducts with DNA (primarily at guanine N7); Induction of intra- and interstrand DNA cross-links; Disruption of DNA helix, inhibiting replication and transcription; Triggering cell cycle arrest and apoptosis[2][5][6][7]