DNA-cisplatin adduct (Pt-DNA adduct)

DNA-cisplatin adducts are the primary cytotoxic lesions formed when the chemotherapy drug cisplatin enters a cell and binds covalently to DNA. These adducts primarily consist of 1,2-intrastrand d(GpG) and d(ApG) crosslinks, which cause significant bending and unwinding of the DNA double helix (PubChem CID 84691). This structural distortion interferes with essential cellular processes such as DNA replication and RNA transcription by stalling polymerase enzymes (StatPearls, Cisplatin). The presence of these adducts triggers various cellular signaling pathways, including the DNA damage response and eventually apoptosis, particularly in rapidly dividing cancer cells (Nature Reviews Cancer, 2007). However, the efficacy of cisplatin is often limited by the cell's ability to repair these adducts through mechanisms like nucleotide excision repair (NER) or by the development of bypass mechanisms (PubMed: 17127063). Understanding the formation and persistence of these adducts is crucial for predicting patient response and overcoming platinum resistance in clinical oncology (PubMed: 21670454).

Other names

Cisplatin-DNA crosslinkPlatinum-DNA adductIntrastrand crosslinkInterstrand crosslinkCis-diamminedichloroplatinum(II)-DNA complex

Cisplatin acts as a DNA-damaging agent by forming covalent bonds with the N7 atoms of purine bases, leading to the formation of DNA-cisplatin adducts. These adducts, mainly 1,2-intrastrand crosslinks, induce a sharp bend in the DNA template, which blocks the progression of DNA and RNA polymerases (StatPearls, Cisplatin). This blockage leads to the activation of DNA repair pathways or, if the damage is irreparable, the induction of p53-mediated apoptosis (PubChem CID 84691).