Platinum–DNA adduct (cross-linking and alkylation)

Platinum–DNA adducts are covalent DNA lesions formed by the binding of platinum-based chemotherapy drugs (such as cisplatin, carboplatin, and oxaliplatin) to DNA, primarily at the N7 position of guanine residues[2][3][6][7]. This binding results in intrastrand and interstrand cross-links or, less frequently, monoadducts, which distort the DNA double helix and disrupt essential cellular processes such as DNA replication and transcription[2][3][6][7]. The resulting DNA damage activates the DNA damage response, leading to cell cycle arrest and triggering cell death pathways including apoptosis and, under some circumstances, necroptosis or autophagy[1][2][3]. While platinum–DNA adducts are the key mediators of the cytotoxicity and anti-tumor efficacy of platinum drugs, the effectiveness of these drugs is limited by significant toxicities and the development of drug resistance, often related to enhanced DNA repair capacity or altered drug transport and detoxification in tumor cells[3][6][7]. Additional note: “DNA adduct cross-linking/alkylation via platinum-DNA binding” is not a canonical target molecule or receptor, but describes a mechanism of action for a chemical class of drugs. It is a reaction/process, not a protein, gene, receptor, or enzyme, and thus not a direct therapeutic target. The actual molecular target is DNA itself, with the function being a chemically induced modification of DNA structure and function by platinum-based chemotherapeutics[2][3][6][7][1].

Other names

Platinum–DNA cross-linkPlatinum–DNA bindingDNA–platinum adductDNA–platinum cross-linkDNA alkylation by platinumPlatinum-induced DNA lesion

Formation of intrastrand and interstrand DNA cross-links by platinum compound binding to the N7 position of guanine bases, leading to changes in DNA structure and function[2][3][6][7]. Inhibition of DNA replication and transcription, causing cell cycle arrest and triggering programmed cell death mechanisms such as apoptosis or necroptosis[1][2][3]. Induction of DNA damage response and disruption of DNA repair pathways, especially when damage overwhelms repair capacity[3][6].