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The cellular DNA replication and transcription machinery is a sophisticated assembly of enzymes and proteins dedicated to the fundamental processes of genome duplication and gene expression (Frontiers in Molecular Biosciences, 2019). This system includes the replisome, which carries out DNA replication, and the transcription complex, centered around RNA polymerases, which synthesizes RNA from DNA templates (NIH, 2024). Key components include DNA polymerases, RNA polymerases, helicases (such as the MCM complex), topoisomerases, and sliding clamps like PCNA (MDPI, 2023). Because cancer cells exhibit uncontrolled proliferation and high metabolic demands, they are heavily dependent on the hyperactivation of this machinery, making it a cornerstone of oncology therapeutics (Frontiers in Molecular Biosciences, 2019). Drugs targeting these processes include antimetabolites that deplete nucleotide pools, topoisomerase inhibitors that induce DNA breaks, and polymerase inhibitors that terminate chain elongation (NIH, 2024). However, because these processes are also essential for normal cell turnover, therapies often result in significant systemic toxicities, such as myelosuppression and gastrointestinal distress (StatPearls, 2023).
Inhibition of DNA and RNA polymerases, topoisomerase poisoning, DNA intercalation, DNA cross-linking, and depletion of nucleotide pools.
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