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Selectivity of DNA Replication: The Importance of Base-Pair Geometry over Hydrogen Bonding.

The polymerase enzyme hardly differentiates between thymine and difluorotoluene nucleotides with respect to the replication selectivity. X-ray structure analysis show the importance of the Watson-Crick geometry for the replication fidelity; base selection is determined by the spatial prerequisite of the substrate pocket and directed protein interactions in the minor groove (schematically shown on the right).