Nuclear DNA (DNA) (DNA)

Nuclear DNA is the primary repository of genetic information in eukaryotic cells and serves as the fundamental molecular target for platinum-based chemotherapeutic agents like oxaliplatin (StatPearls, NBK542163). Oxaliplatin exerts its anti-tumor activity by forming covalent bonds with DNA bases, specifically creating 1,2-intrastrand crosslinks between adjacent guanine residues (PubChem, CID 43805). These platinum-DNA adducts cause significant structural distortion of the double helix, which physically blocks the progression of DNA and RNA polymerases. In rapidly dividing tumor cells, these lesions lead to replication fork stall, DNA strand breaks, and the activation of apoptotic signaling pathways (PubMed, 17513805). While highly effective in treating malignancies such as colorectal cancer, the non-specific targeting of DNA in all proliferating cells contributes to systemic toxicities, including neurotoxicity and bone marrow suppression (NIH, NCI Dictionary).

Other names

Genomic DNADeoxyribonucleic acidNuclear genomeChromosomal DNA

Oxaliplatin undergoes non-enzymatic conversion into active derivatives that covalently bind to the N7 position of guanine and adenine residues in nuclear DNA. This binding forms 1,2-intrastrand crosslinks, 1,3-intrastrand crosslinks, and interstrand crosslinks, which physically impede DNA polymerases and RNA polymerases, triggering cell cycle arrest and inducing apoptosis (StatPearls, NBK542163; PubChem, CID 43805).