DNA crosslinking and damage induction via platinum adduct (null)

**DNA crosslinking and damage induction via platinum adduct** refers to the process by which platinum-based chemotherapeutic agents—most notably cisplatin, carboplatin, and oxaliplatin—form covalent bonds with nuclear DNA. These drugs create a variety of **DNA lesions**, including intrastrand and interstrand crosslinks as well as bulky monoadducts. The most common lesion is the intrastrand guanine–guanine crosslink (>70% for cisplatin), which distorts the double helix structure. These modifications block essential processes such as **DNA replication** and **transcription**, ultimately triggering cell cycle arrest or apoptosis if not repaired. Cells attempt to remove these lesions primarily through nucleotide excision repair (NER) pathways; proteins such as ERCC1 are critical for this process. Deficiencies or variations in these repair mechanisms can influence both drug sensitivity and resistance in tumors. Overexpression or increased activity of NER components is associated with clinical resistance to platinum drugs. While this mechanism is central to the antitumor efficacy of several widely used chemotherapies, it also underlies their dose-limiting toxicities—including nephrotoxicity, neurotoxicity, ototoxicity—and contributes significantly to acquired drug resistance during cancer treatment[2][4][6]. **Note:** This entry describes a *mechanism* rather than a discrete molecular target such as an enzyme or receptor; thus it does not fit standard definitions for "therapeutic target" classification. It represents a pharmacodynamic effect rather than a single protein/gene product[1].

Other names

Platinum-DNA adduct formationPlatinum-induced DNA crosslinkingCisplatin-DNA adductsPlatinum-based DNA damage

Formation of covalent platinum-DNA adducts (intrastrand and interstrand crosslinks) - Induction of bulky lesions that distort the DNA helix and block replication/transcription machinery[1][3][6] - Activation of cellular apoptosis pathways due to irreparable DNA damage[2][3]