Cytotoxic DNA cross-linking

Cytotoxic DNA cross-linking refers to the formation of covalent bonds between two nucleotides within the same strand or across complementary strands of double-stranded DNA. This process can also involve proteins covalently linked to DNA ("DNA-protein crosslinks"). Such lesions are highly disruptive because they block essential cellular processes like replication and transcription. If unrepaired, these lesions lead to cell cycle arrest and cell death. The cytotoxicity is exploited therapeutically in cancer treatment by using agents such as alkylating agents, platinum-based drugs, mitomycin C, psoralens, and topoisomerase inhibitors. These drugs induce lethal damage preferentially in rapidly dividing cancer cells but can also harm normal proliferative tissues. While "cytotoxic DNA cross-linking" describes a mechanism rather than a discrete molecular target or receptor protein/complex—unlike enzymes or receptors—it is central as an anti-cancer strategy.

Other names

DNA crosslinkingDNA-protein crosslinkingDNA interstrand crosslinkingDPC (for "DNA-protein crosslinks")

Covalent binding to nucleotides in DNA to form intra-strand or inter-strand links that block replication and transcription; Trapping topoisomerases on DNA to prevent re-ligation during the repair process.