DNA crosslinking (causing DNA damage)

DNA crosslinking refers to the formation of covalent bonds between two nucleotide residues within a single strand (intrastrand) or across opposite strands (interstrand) of the double helix. Crosslinks can also occur between DNA and proteins ("DNA-protein crosslinks"). These lesions are highly disruptive because they block essential cellular processes like replication and transcription; if unrepaired, they lead to cell death or genomic instability. Endogenous sources include reactive oxygen species and aldehydes generated during metabolism; exogenous sources include chemotherapeutic drugs such as alkylating agents (e.g., cisplatin), radiation, tobacco smoke components, and certain food additives.[1][2][3][4][5] While not a molecular target itself—rather a type of lesion—inducing DNA crosslinks is an established therapeutic strategy, especially in oncology. The cytotoxicity arises from the inability of cells to accurately replicate or transcribe their genomes when faced with persistent interstrand or protein-DNA adducts. Multiple repair pathways exist for resolving these lesions; defects in these pathways increase sensitivity both to endogenous damage and chemotherapeutic agents.[1][2] Because "DNA crosslinking causing DNA damage" describes a process rather than a discrete molecule/receptor/target protein/gene/family typically catalogued as drug targets—and because it encompasses multiple types of chemical modifications—it should not be considered a canonical therapeutic target but rather an important mechanism underlying both disease pathology and drug action. If you require structured information on specific enzymes involved in repairing these lesions—such as SPRTN protease or tyrosyl-DNA phosphodiesterases—they would each have their own canonical entries.[1][2]

Other names

DNA interstrand crosslinkDNA intrastrand crosslinkDNA-protein crosslinkDPC (for "DNA-protein crosslink")ICL (for "interstrand crosslink")

Drugs that induce DNA crosslinks act by covalently linking nucleotides within or between strands of the double helix, thereby blocking essential processes such as replication and transcription, leading to cell cycle arrest and apoptosis. This cytotoxic effect is exploited in chemotherapy for cancer treatment, where rapidly dividing cells are particularly susceptible to these lesions.[3][4][5]