Replication of non-hydrogen bonded bases by DNA polymerases: A mechanism for steric matching

Recent experiments have presented evidence that Watson-Crick hydrogen bonds in a base pair are not absolute requirements for efficient synthesis of th at pair by DNA polymerase enzymes. Here we examine quantitative steady-stat e kinetic data from several published studies involving poorly hydrogen-bon ding UNA base analogues and adducts, and analyze the results in terms of so lvation, hydrogen bonding, and steric effects. We propose a mechanism that can explain the surprising lack of hydrogen-bonding requirement accompanied by significant selectivity in pairing. This hypothesis makes use of steric matching, enforced both by the tightly confined polymerase active site and by the DNA backbone, as a chief factor determining nucleotide selection du ring DNA synthesis. The results also suggest that hydrogen bonds from bases to water (solvation) may be important in increasing the effective size of DNA bases, which may help prevent misinsertion of small bases opposite each other. (C) 1998 John Wiley & Sons, Inc.