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Cellular DNA and RNA polymerases are a broad class of enzymes essential for the synthesis of nucleic acids, encompassing DNA-directed DNA polymerases and DNA-directed RNA polymerases. DNA polymerases, such as Pol alpha, delta, and epsilon, are responsible for genome replication and repair, ensuring genetic stability across cell generations [Hübscher et al., 2002]. RNA polymerases, including Pol I, II, and III, catalyze the transcription of DNA into various RNA species required for protein synthesis and cellular regulation [Cramer, 2019]. These enzymes are critical therapeutic targets in oncology, where inhibitors like cytarabine and gemcitabine act as antimetabolites to disrupt DNA synthesis in rapidly dividing cancer cells [Kaufman et al., 1991]. Additionally, novel inhibitors like CX-5461 specifically target RNA polymerase I to treat advanced hematologic and solid tumors [Drygin et al., 2011]. However, because these enzymes are fundamental to all cellular life, drugs targeting them often carry significant safety concerns, including myelosuppression and systemic toxicity, due to their impact on healthy proliferating tissues [StatPearls, 2023].
Competitive inhibition of nucleotide binding, DNA chain termination following incorporation, and template blocking via DNA intercalation.
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