DNA crosslinking via platinum-DNA adduct formation

DNA crosslinking via platinum-DNA adduct formation refers to the process by which platinum-based chemotherapeutic agents such as cisplatin bind covalently to DNA. The most common lesion is the 2d(pGpG) [Pt-(GG)] intrastrand crosslink, representing over 70% of total platination events. These lesions disrupt normal cellular processes by impairing both replication and transcription. If not repaired—primarily through nucleotide excision repair mechanisms—they can trigger apoptotic pathways leading to cell death. This mechanism underlies the anticancer efficacy of drugs like cisplatin but also contributes to dose-limiting toxicities such as peripheral neuropathy when these lesions accumulate in non-cancerous tissues like dorsal root ganglia.

Other names

Platinum-DNA adductCisplatin-induced DNA crosslinkPt-DNA adductPlatinum-based DNA lesion

Formation of covalent platinum-DNA adducts, primarily intrastrand and interstrand crosslinks, which block DNA replication and transcription, leading to cell cycle arrest and apoptosis