DNA cross-linking via platinum-DNA adduct

Platinum-based anticancer drugs such as cisplatin and carboplatin exert their cytotoxic effects primarily by forming covalent bonds with purine bases on DNA, resulting in the formation of platinum–DNA adducts. These lesions include both intra-strand and inter-strand cross-links that distort the DNA helix. The presence of these bulky lesions inhibits essential cellular processes such as transcription elongation by RNA polymerase II[1], stalls replication forks[2], and triggers recruitment of the cellular DNA damage response machinery. If unrepaired—primarily through nucleotide excision repair pathways—these persistent lesions can lead to cell cycle arrest or programmed cell death (apoptosis), which underlies their therapeutic effect against rapidly dividing cancer cells[3][4]. However, accumulation or persistence of these adducts in normal tissues is associated with significant toxicities. Note: This entry is marked as "is_incorrect" because "DNA cross-linking via platinum-DNA adducts" describes a **mechanism** rather than a discrete molecular target like a protein or receptor. It refers to a type of chemical modification inflicted on genomic DNA rather than an endogenous biomolecule; thus it does not fit standard definitions for canonical drug targets such as receptors or enzymes.

Other names

Platinum-DNA adductPt–DNA adductcisplatin-DNA adductcarboplatin-DNA adduct

Formation of covalent platinum–DNA cross-links that block DNA replication and transcription, leading to cell cycle arrest and apoptosis[1][2][3][4]