DNA crosslinking damage

DNA crosslinking damage refers to the formation of covalent bonds between two nucleotides within the same strand (*intrastrand*) or across complementary strands (*interstrand*) of double-stranded DNA. This can also include covalent links between proteins and DNA (*DNA-protein crosslinks*). Such lesions are caused by exogenous agents like chemotherapeutic drugs (e.g., platinum compounds), radiation, reactive oxygen species, aldehydes, and certain metabolites. Crosslinks block essential cellular processes such as replication and transcription; if left unrepaired they trigger cell death. Cells have evolved complex repair mechanisms involving nucleotide excision repair pathways, homologous recombination factors such as BRCA1/WRN helicase complexes in eukaryotes,[1] specialized proteases like SPRTN for DPCs,[2] translesion synthesis polymerases,[3] and other enzymes. While these lesions are highly toxic to cells—making them useful in cancer chemotherapy—they are not themselves molecular targets but rather types of molecular damage that drugs aim to induce. Therefore "DNA crosslinking/damage" is not considered a canonical therapeutic target like an enzyme or receptor; it is better described as a *therapeutic mechanism* exploited by certain drugs.[1][3] If you need structured information about specific proteins involved in recognizing or repairing this type of damage—such as XPF–ERCC1 endonuclease complex, FANCI/D2 complex from Fanconi anemia pathway,[3] SPRTN protease,[2] etc.—those would be valid molecular targets with their own canonical names.

Other names

DNA crosslinkingDNA interstrand crosslinkDNA intrastrand crosslinkDNA-protein crosslink (DPC)

Drugs induce covalent bonds between nucleotides on the same or opposite strands of DNA ("crosslinks"), blocking replication and transcription and leading to cell death if unrepaired[1][3].