DNA Polymerase β: Closing the Gap between Structure and Function

DNA polymerase (dpol) β has served as a model for structural, kinetic, and computational characterization of the DNA synthesis reaction. The laboratory directed by Samuel H. Wilson has utilized a multifunctional approach to analyze the function of this enzyme at the biological, chemical, and molecular levels for nearly 50 years. Over this time, it has become evident that correlating static crystallographic structures of dpol β with solution kinetic measurements is a daunting task. However, aided by computational and spectroscopic approaches, novel and unexpected insights have emerged. While dpols generally insert wrong nucleotides with similar poor efficiencies, their capacity to insert the right nucleotide depends on the identity of the dpol. Accordingly, the ability to choose right from wrong depends on the efficiency of right, rather than wrong, nucleotide insertion. Structures of dpol β in various liganded forms published by the Wilson laboratory, and others, have provided molecular insights into the molecular attributes that hasten correct nucleotide insertion and deter incorrect nucleotide insertion. Computational approaches have bridged the gap between structures of intermediate complexes and provided insights into this basic and essential chemical reaction.