DNA cross-linking via platinum agent

DNA cross-linking via platinum agent refers not to a single molecular target but rather to the formation of covalent bonds between certain chemotherapeutic agents containing platinum—notably cisplatin, carboplatin, and oxaliplatin—and specific sites within cellular DNA. These drugs bind primarily at the N7 position on guanine residues in the genome. The resulting lesions include intrastrand and interstrand crosslinks, as well as DNA-protein crosslinks. The most common lesion is the 1,2-intrastrand d(GpG) adduct formed by cisplatin. These modifications cause significant distortion in the double helix structure that blocks essential processes such as replication and transcription. If unrepaired by cellular mechanisms like nucleotide excision repair or homologous recombination pathways, these lesions trigger apoptosis—a key mechanism underlying their antitumor activity. While "DNA cross-linking via platinum agent" is not a canonical molecular target like an enzyme or receptor but rather describes a class of drug-induced chemical modifications on nucleic acids that serve as critical cytotoxic lesions for cancer therapy. Thus it is considered an indirect therapeutic target. Note: This entry is marked is_incorrect = true because it does not refer to a discrete biomolecule but instead describes a process/lesion type induced by drugs; this may be too broad or imprecise for structured databases focused on proteins/genes/receptors. However, it remains highly relevant mechanistically for oncology drug action. If you need information mapped specifically onto individual proteins involved in recognition/repair (e.g., ERCC1), those would be separate entries under their respective names.

Other names

DNA-platinum adductPlatinum-induced DNA crosslinkPlatinum-DNA adductPt-DNA crosslinkCisplatin-DNA adduct

Formation of covalent bonds between platinum and the N7 position of purine bases in DNA (mainly guanine), leading to mono-adducts, intrastrand and interstrand crosslinks. Crosslinks distort the double helix structure, block replication and transcription machinery. Induction of cell death when repair mechanisms are overwhelmed or fail.