DNA Crosslinking via Platinum Compounds

DNA crosslinking via platinum compounds refers to the process by which platinum-based chemotherapeutic agents, such as cisplatin, form covalent bonds between DNA strands or between DNA and proteins. This crosslinking disrupts essential cellular processes like replication and transcription, leading to cytotoxicity and cell death. Platinum compounds primarily induce intrastrand crosslinks, interstrand crosslinks, and DNA-protein crosslinks (DPCLs). Cells recognize these lesions as severe damage, activating DNA repair pathways such as nucleotide excision repair (NER), homologous recombination (HR), base excision repair (BER), mismatch repair (MMR), and non-homologous end joining pathways. Tumor resistance often arises from enhanced capacity for lesion recognition/repair or increased drug efflux. Platinum-induced DNA crosslinking underpins the efficacy of drugs like cisplatin against various cancers. However, resistance due to efficient repair mechanisms remains a major clinical challenge.

Other names

Platinum-induced DNA crosslinkingCisplatin-induced DNA damageDNA adduct formation by platinum compounds

Formation of DNA adducts (intrastrand, interstrand, and DNA-protein crosslinks) that disrupt DNA replication and transcription.