Structural insights into the origins of DNA polymerase fidelity.
DNA polymerases discriminate from a pool of structurally similar molecules to insert the correct nucleotide to preserve Watson-Crick base pairing rules. The ability to choose between "right and wrong" is highly dependent on the identity of the polymerase. Because naturally occurring polymerases with divergent fidelities insert incorrect nucleotides with comparable efficiencies, fidelity is primarily governed by the ability to insert the correct nucleotide. DNA polymerases generally bind the correct nucleotide with similar affinities, but low-fidelity polymerases insert correct nucleotides more slowly than higher fidelity enzymes. A comparison of crystallographic ternary substrate complexes of DNA polymerases from five families exhibiting a range of nucleotide insertion rates reveals possible structural features that lead to rapid, efficient, and faithful DNA synthesis.
Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
William A
WA
Beard
Samuel H
SH
Wilson
D000818:Animals; D004261:DNA Replication / Q000502:physiology*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans
D004259:DNA-Directed DNA Polymerase