DNA cross-link (cisplatin-induced) (null)

Cisplatin exerts its anticancer effects primarily by binding to nuclear DNA and forming covalent platinum-DNA adducts. The most common lesions are 1,2-intrastrand cross-links between adjacent guanine bases (~90% of adducts), but interstrand cross-links and monoadducts also occur[5][6][7]. These bulky lesions distort the helical structure of the double helix—unwinding it locally—and block essential processes such as replication and transcription. The resulting stalled cell cycle triggers apoptosis in rapidly dividing cancer cells. Cells respond by activating various repair pathways; however, if the damage is irreparable or overwhelming, programmed cell death ensues. Cisplatin can also form ternary complexes with both DNA and proteins ("DNA-protein cross-links"), which are even more persistent obstacles for cellular repair machinery than simple intrastrand adducts[1]. Only a small fraction (~1%) of intracellular cisplatin binds nuclear DNA; much interacts with cytoplasmic nucleophiles such as glutathione or mitochondrial components—contributing further to cytotoxicity through oxidative stress mechanisms[6]. While "DNA cross-linking/DNA damage induction" describes a process rather than a discrete molecular target like an enzyme or receptor, it remains central to the therapeutic action—and toxicity—of platinum-based chemotherapies. Thus this entry does not represent a canonical drug target but rather a class of critical drug-induced macromolecular lesions. **Note:** This entry is considered "incorrect" as a canonical therapeutic target because it refers to a type of chemical lesion/process rather than an individual molecule/protein/receptor typically cataloged as drug targets.

Other names

Cisplatin-induced DNA cross-linkCisplatin-mediated DNA damagePlatinum-DNA adductsDNA-platinum cross-link

Formation of covalent bonds between platinum and purine bases on DNA, leading to intra-strand and inter-strand cross-links[5][6][7]