DNA Polymerase Selectivity: Sugar Interactions Monitored with High-Fidelity Nucleotides

The essential prerequisite of any organism is to keep its genome intact and to accurately duplicate it before cell division. All DNA synthesis required for DNA repair, recombination, and replication depends on the ability of DNA polymerases to recognize the template and correctly insert the complementary nucleotide. In a current model, fidelity is achieved by the ability of DNA polymerases to edit nucleobase pair shape and size.PI This model is supported by crystal structures of DNA polymerases that suggest the formation of nucleotide binding pockets, which exclusively accommodate Watson Crick base pairs.(2] Nevertheless, structural data of DNA polymerases complexed with the DNA substrates and a noncanonical triphosphate, which would be very helpful for gaining insights into the causes of error-prone DNA synthesis, have at present not been reported. Thus, functional studies of DNA polymerases with nucleotide analogues have been shown to be extremely valuable)l) Since most functional studies have focused on nucleobase recognition processes,P] little is known about the