Platinum-DNA adduct (Pt-DNA adduct)

Cisplatin and related platinum compounds function by crossing cellular membranes and binding covalently to DNA, with a preference for guanine residues at the N7 position[3]. The predominant DNA adducts are intra-strand crosslinks (especially at GG and AG sequences), as well as inter-strand crosslinks and mono-adducts[3][5]. These platinum-DNA adducts bend and unwind the DNA helix, physically blocking the action of DNA polymerases and transcription machinery[3][4][5]. The resulting DNA damage activates the cell's nucleotide excision repair pathways; failure to repair the lesions results in cell cycle arrest and apoptosis[3][4]. Platinum-DNA adduct quantification is a pharmacodynamic biomarker for predicting therapeutic efficacy and toxicity[4]. Platinum-DNA adduct formation is the primary mechanism underlying both the antitumor effectiveness and the dose-limiting side effects of platinum-based chemotherapy[3][4][5][6]. This target is thus best described as a DNA modification (platinum-DNA adduct) that serves as the direct molecular target for certain anticancer drugs, rather than a classical receptor or enzyme[3][4][5]. The query, as written, is incorrect in that it implies "DNA replication process" is a direct target, when the actual target is the formation of platinum-DNA adducts disrupting this process.

Other names

Cisplatin-DNA adductTransplatin-DNA adductPlatinum-DNA crosslinkPt-DNA adduct

Formation of covalent intra- and inter-strand crosslinks in DNA. Stalling of replication and transcription machinery through physical DNA distortion. Activation of cell cycle checkpoints and apoptosis in rapidly dividing cells. Induction of DNA damage response and repair mechanisms.