METAL IONS AND INFORMATION TRANSFER--MECHANISM OF RNA SYNTHESIS

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The effects of metal ions on nucleic acids structure and function have been determined. The primary focus is now on the mechanism of RNA synthesis at the active site of RNA polymerase. The geometry of interaction at the active site of the enzyme is being probed during the transcription process to determine how this geometry changes during transcription and affects its operation. A comprehensive mechanism for assuring fidelity in copying the genetic code has been developed which depends on the sensing by the polymerase of the complementarily between the DNA base and the base of the incoming nucleoside triphosphate. The polymerase shifts its conformation to prevent bond formation when the substrate is not complementary, while the enzyme otherwise remains in the proper conformation for bond formation to allow efficient polymerization with the correct base. The structural model is being applied to understand the effect of DNA damage, promoters, and transcription factors on transcription.