DNA interstrand cross-linking via alkylation (null)

DNA strand cross-linking via alkylation is a cytotoxic process where DNA bases (commonly guanine) are covalently connected either within a strand (intrastrand) or across both strands (interstrand), thereby blocking replication and transcription and leading to cell death[1][2][3][4][5][7]. This process is exploited pharmacologically in oncology—many chemotherapeutic drugs are engineered or selected for their ability to form DNA cross-links and thereby trigger cancer cell apoptosis. However, DNA cross-linking is not a protein, gene, or classical receptor; rather, it is a chemical modification event and thus is best classified as "Other" under molecular classification. It is a therapeutic target by virtue of being the intended action of alkylating anti-cancer drugs, but not in the sense of traditional drug targets like receptors or enzymes. The main therapeutic challenges include genomic instability, mutagenesis, and non-selective cytotoxicity, which limits safe dosing and increases the risk of secondary malignancies or organ damage[1][3][4][5][7]. This cross-linking, when not repaired, ultimately leads to DNA damage response activation, cell cycle arrest, and various forms of cell death including apoptosis and necrosis, particularly in rapidly dividing cells such as cancer cells[7].

Other names

DNA crosslinking via alkylationDNA alkylation and cross-linkingInterstrand DNA cross-linking

Alkylating and cross-linking DNA bases, especially guanine; Preventing strand separation and DNA replication; Triggering apoptosis by causing irreparable genomic damage