DNA/RNA crosslinking via alkylation

DNA/RNA crosslinking via alkylation refers to the chemical process where exogenous or endogenous agents transfer an alkyl group onto nucleophilic sites within nucleotide bases on either DNA or RNA. This leads to the formation of covalent bonds between two strands (interstrand) or within one strand (intrastrand), severely disrupting essential cellular processes such as replication and transcription. The resulting lesions can trigger cell cycle arrest and apoptosis if unrepaired. Alkylating agents capable of inducing these lesions have been widely used as chemotherapeutics—most notably nitrogen mustards, platinum-based drugs like cisplatin, mitomycin C, psoralens, and others—because they preferentially kill rapidly dividing cells such as those found in cancers. However, their lack of selectivity also underlies significant side effects including bone marrow suppression and risk for secondary cancers.

Other names

DNA crosslinking via alkylationRNA crosslinking via alkylationAlkylating agent-induced nucleic acid crosslinksNucleic acid cross-link formation (alkylating)

Drugs targeting this process act primarily by transferring an alkyl group to nucleophilic sites on DNA or RNA bases, leading to covalent interstrand or intrastrand links that block replication and transcription. This results in cytotoxicity due to failed repair and cell death—especially effective against rapidly dividing cancer cells. Some agents also induce DNA-protein or RNA-protein crosslinks.