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DNA polymerase is an enzyme that synthesizes DNA from deoxyribonucleotide triphosphates, using a template strand to ensure accurate DNA replication and repair. Therapeutic targeting exploits its crucial role in replication and repair, notably in cancer and viral infections. Ribonucleotide reductase is the rate-limiting enzyme responsible for the conversion of ribonucleotides to deoxyribonucleotides, the essential substrates for DNA synthesis and repair; its activity is tightly regulated and integral for maintaining balanced dNTP pools. Both enzymes are critical for cell proliferation, and their inhibition forms the basis for multiple classes of anti-cancer and antiviral drugs.
Inhibitors of DNA polymerase act primarily as nucleoside/nucleotide analogs causing chain termination or inhibiting DNA synthesis; some are DNA damaging agents; others target specific polymerases (replication vs repair). RNR inhibitors include substrate analogs (e.g., gemcitabine), free radical scavengers (e.g., hydroxyurea), and compounds that inhibit subunit interaction or cofactor activity.
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