DNA crosslinking and damage via platinum adducts

DNA crosslinking and damage via platinum adducts is not a single molecular target but rather describes the chemical lesions formed when platinum-based chemotherapeutic agents such as cisplatin bind covalently to nuclear DNA. These drugs form both intrastrand and interstrand crosslinks by creating stable platinum-DNA adducts. The most common lesion is the 1,2-intrastrand d(GpG) crosslink. These modifications distort the structure of the double helix, block essential processes like replication and transcription, activate cellular stress responses including apoptosis, and ultimately lead to cell death if unrepaired[1][2]. Cells attempt to repair these lesions primarily through nucleotide excision repair (NER), homologous recombination (HR), Fanconi anemia pathway components for interstrand links, translesion synthesis polymerases for bypassing lesions during replication, as well as other endonucleases[5]. Overexpression or increased activity in these pathways can confer resistance to platinum drugs—a major clinical challenge in oncology. Key biomarkers associated with response include ERCC1 mRNA/protein levels; high expression correlates with drug resistance due to more efficient removal of toxic adducts[3].

Other names

Platinum-induced DNA damagePlatinum-DNA adductsCisplatin-DNA adductsPlatinum-based DNA crosslinks

Formation of covalent platinum-DNA adducts that cause intra-strand and inter-strand crosslinks, leading to distortion of the DNA helix, blocking replication and transcription, and triggering cell death pathways[1][2][3][4][5].