DNA cross-link (leading to inhibition of DNA replication and transcription) (None commonly used; sometimes abbreviated as "DNA cross-link" or "ICL" (for interstrand cross-link) in literature, but no universal abbreviation.)

A DNA cross-link refers to the formation of covalent bonds either between two strands within the same molecule (intrastrand) or across complementary strands (interstrand)—or between DNA and proteins (DNA-protein crosslinks, DPCs). These lesions physically block essential processes such as replication and transcription, because they prevent unwinding/separation required by polymerases. Many anticancer agents exploit this vulnerability by inducing such lesions selectively in rapidly dividing cells. However, these are not classical drug targets themselves but rather sites/mechanisms where drugs exert their cytotoxic effects. Unrepaired lesions can lead to cell death via apoptosis but also contribute to mutagenesis if bypassed inaccurately during repair attempts.[3][1]

Other names

DNA interstrand cross-linkDNA intrastrand cross-linkDNA-protein crosslink (DPC)ICL (interstrand crosslink)DPC (DNA-protein crosslink)

Drugs targeting this process act by: - Forming covalent bonds between two strands of the DNA double helix (interstrand) or within one strand (intrastrand), preventing strand separation required for replication and transcription. - Trapping proteins on the DNA via covalent linkage (DNA-protein crosslinks), stalling polymerases and blocking progression through S phase. - Inducing cytotoxicity through persistent blockage leading to double-strand breaks if unrepaired during attempted replication/transcription[1][5].