Kornberg is best known for his discovery (with Severo Ochoa) of "the mechanisms in the biological synthesis of deoxyribonucleic acid (DNA)", including the isolation of DNA polymerase I, which led to his Nobel prize. He was the first scientist to make DNA in a test tube. He also studied pathways for synthesis of ATP and nucleotides, and he was the first to synthesize PRPP. In his later years, Kornberg studied inorganic polyphosphates.
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