DNA–platinum adduct

DNA–platinum adducts are covalent modifications of DNA formed when platinum-based chemotherapy drugs (such as cisplatin, carboplatin, or oxaliplatin) undergo aquation inside the cell, generating reactive species that coordinate preferentially to the N7 atom of guanine bases in DNA. These lesions include monofunctional adducts, bifunctional intrastrand cross-links (mainly between adjacent guanine or AG bases), and (rarely) interstrand cross-links. The local DNA distortion caused by these adducts blocks essential biomolecular processes like replication and transcription, stalling polymerases and triggering DNA damage responses that result in programmed cell death (apoptosis). The amount, type, and persistence of these adducts are influenced by DNA structural context, nucleosome positioning, drug structure, and repair activity. They are central to the mechanism of platinum drug cytotoxicity in cancer treatment, but also underlie dose-limiting side effects due to DNA damage in normal tissues[1][2][3]. If you need to map this to protein or gene targets, note that platinum–DNA adducts are a chemical modification of DNA and do not correspond to a specific protein, receptor, enzyme, or gene, but are the principal structural lesions recognized for the mechanism of action of platinum drugs.

Other names

platinum–DNA adductDNA–platinum complexcisplatin–DNA adductplatinum adduct

Platinum drugs form covalent bonds with the N7 position of guanine in DNA, resulting in monofunctional (single attachment) or bifunctional (cross-linked) adducts. Intrastrand and interstrand cross-linking distort the DNA double helix, predominantly at GG or AG dinucleotides, causing strong local kinks and blocking access by polymerases and other DNA-processing enzymes[1][3]. The DNA lesion stalls replication and transcription machinery (notably RNA polymerase II), ultimately triggering apoptosis and cell death[1][2].