DNA crosslinking and DNA damage induction via platinum adducts

DNA crosslinking and DNA damage induction via platinum adducts is not a single molecular target but rather describes the cellular process by which platinum-based chemotherapeutic agents—such as cisplatin, carboplatin, and oxaliplatin—exert their cytotoxic effects. These drugs form covalent bonds with nucleophilic sites on the purine bases within nuclear DNA, resulting in various types of DNA lesions, most notably: * Intrastrand crosslinks (~70% for cisplatin), primarily between adjacent guanine residues. * Interstrand crosslinks that link opposite strands. * Monofunctional adducts. * Ternary complexes involving both protein and DNA ("DNA-protein cross-links")[1][5]. These structural changes distort the double helix, block essential processes like replication and transcription, activate cellular stress responses including apoptosis pathways, and ultimately lead to cell death if unrepaired. The primary repair pathway for these lesions is nucleotide excision repair (NER), with proteins such as ERCC1 playing key roles; defects or variations in these pathways can influence both drug sensitivity/resistance profiles[2][3][4]. Overexpression or enhanced activity of certain repair proteins can confer resistance to platinum drugs. This entry does not represent a canonical therapeutic "target" like an enzyme or receptor but rather a mechanistic class describing how certain drugs interact with cellular macromolecules to achieve their effect. Therefore it should be flagged as incorrect if used where a specific molecular target is required.

Other names

Platinum-DNA adduct formationPlatinum-induced DNA crosslinkingCisplatin-DNA adductsPlatinum-based DNA damage

Formation of covalent platinum-DNA adducts leading to intra-strand and inter-strand crosslinks[1][3][7] Disruption of normal DNA structure, blocking replication and transcription[2][3]