DNA alkylation and crosslinking site

DNA alkylation/crosslinking sites are locations within genetic material where electrophilic drugs or xenobiotic compounds chemically modify DNA nucleobases, most commonly via addition of alkyl groups or formation of inter- or intrastrand crosslinks. Such modification blocks DNA replication and transcription, triggering cell cycle arrest and cell death if unrepaired, which is exploited by certain chemotherapeutic agents for cancer treatment[1][2][3]. Therapeutic use of DNA modifying agents centers on their ability to selectively kill rapidly dividing cells but also poses significant safety risks, including off-target toxicity and long-term mutagenesis, while resistance can occur through DNA repair pathway activation[5][7]. Many anticancer drugs intentionally target these lesions, with crosslinking sites serving as both therapeutic targets and biomarkers for drug activity. However, the term represents chemically altered DNA rather than a distinct molecule or protein, and thus is not a canonical molecular target in typical biomarker or drug-target databases.

Other names

DNA crosslinking siteDNA alkylation siteDNA lesionDNA adductDNA damage site

Covalent binding/alkylation of DNA bases leading to crosslink formation; Blocking DNA strand separation and thereby inhibiting DNA synthesis and cell division; Inducing replication fork stalling and cell death by creating DNA damage