DNA crosslinking by platinum compound

DNA crosslinking by platinum compounds refers to the process where drugs such as cisplatin, carboplatin, or oxaliplatin form covalent bonds with nucleophilic sites on the bases within DNA. These agents primarily create intra-strand and inter-strand links between adjacent guanine residues or between guanine and adenine. The resulting adducts cause significant distortion to the double helix structure—often introducing kinks—which disrupts base stacking, impairs replication and transcription processes, and ultimately leads to cell cycle arrest or apoptosis if not repaired. This mechanism is exploited therapeutically in cancer treatment because rapidly dividing tumor cells are particularly sensitive to these lesions. The effectiveness of platinum-based chemotherapy can be influenced by cellular capacity for nucleotide excision repair; biomarkers such as ERCC1 and BRCA1 are associated with resistance or sensitivity to these drugs. While highly effective against various cancers—including lung cancer—these agents also pose notable safety concerns due to their toxic effects on kidneys, nerves, and bone marrow. Note: "DNA crosslinking by platinum compound" is not itself a molecular target but rather describes a chemical event induced by certain drugs. It does not refer to a specific protein/receptor/enzyme/gene but rather an effect on genomic material; thus it should not be considered a canonical therapeutic target per se.

Other names

Platinum-induced DNA crosslinkPlatinum-DNA adductCisplatin-DNA crosslinkPlatinum-based DNA damage

Formation of covalent bonds between platinum compounds and nucleophilic sites on DNA bases (primarily guanine N7), resulting in intra-strand and inter-strand crosslinks that distort the double helix structure.