DNA crosslinking (via alkylation)

DNA crosslinking (via alkylation) is not a single protein or conventional “target” such as a receptor or enzyme; rather, it refers to a chemical process in which alkylating agents form covalent bonds between two DNA bases, either within a DNA strand (intrastrand) or between strands (interstrand)[1][5][6]. This crosslinking disrupts DNA replication and transcription, leading to cell cycle arrest and cell death. Alkylating agents are widely used as chemotherapeutic drugs for cancer, exploiting the heightened replication and limited repair capabilities of tumor cells. Specific drugs (e.g., nitrogen mustards, platinum compounds, mitomycin C, psoralens, and treosulfan) produce DNA crosslinks by covalently modifying guanine and other nucleophilic nucleotide bases[1][2][3]. These modifications can trigger apoptosis, but also introduce significant toxicities in healthy proliferative tissues and risk mutagenesis[1][5]. DNA crosslinking via alkylation describes a molecular mechanism, not a gene product or single macromolecule[1][5][6].

Other names

DNA interstrand crosslinkingDNA intrastrand crosslinkingDNA alkylationDNA crosslinking

Covalent alkylation of nucleotide bases Crosslinking DNA strands (intra- and interstrand) Prevention of DNA replication and transcription Induction of replication arrest and apoptotic cell death