DNA-cisplatin platinum adducts (DNA-Pt adducts)

DNA-cisplatin platinum adducts are the primary cytotoxic lesions formed when the chemotherapy drug cisplatin binds covalently to genomic DNA (Dasari & Bernard, 2014, PubMed). These adducts consist mainly of 1,2-intrastrand d(GpG) and d(ApG) crosslinks, which induce a sharp bend in the DNA double helix (Galluzzi et al., 2012, Nature Reviews Cancer). This structural distortion interferes with fundamental cellular processes, including DNA replication and transcription, by stalling polymerase enzymes (NCI Drug Dictionary). The presence of these adducts also recruits various damage-recognition proteins, such as High Mobility Group (HMG) box proteins, which can shield the DNA from repair mechanisms or facilitate downstream signaling (Wang & Lippard, 2005, Nature Reviews Drug Discovery). Ultimately, the accumulation of unrepaired DNA-platinum adducts activates apoptotic pathways, leading to the death of rapidly dividing cancer cells (StatPearls, 2023). The clinical efficacy of cisplatin is often limited by the cell's ability to repair these adducts via the nucleotide excision repair (NER) pathway or by the development of cellular resistance mechanisms (Zhu et al., 2023, PubMed). Monitoring the formation and persistence of these adducts serves as a critical indicator of drug efficacy and patient response in various malignancies (PubMed, 2021).

Other names

Cisplatin-DNA adductsPt-DNA crosslinksIntrastrand crosslinksInterstrand crosslinkscis-diamminedichloroplatinum(II)-DNA complex

Cisplatin acts by forming covalent bonds with DNA bases, resulting in DNA-platinum adducts that inhibit DNA synthesis and transcription (StatPearls, 2023). The primary mechanism involves the formation of 1,2-intrastrand crosslinks between adjacent guanine residues, which distorts the DNA structure and prevents the progression of replication forks and RNA polymerase (Galluzzi et al., 2012, Nature Reviews Cancer). This distortion also triggers the recruitment of HMG-domain proteins and activates DNA damage response pathways, leading to cell cycle arrest and apoptosis (Dasari & Bernard, 2014, PubMed).