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Replication of non‐hydrogen bonded bases by DNA polymerases: A mechanism for steric matching
Author(s) -
Kool Eric T.
Publication year - 1998
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(1998)48:1<3::aid-bip2>3.0.co;2-7
Subject(s) - steric effects , chemistry , dna polymerase , hydrogen bond , solvation , base pair , polymerase , dna , dna replication , molecular structure of nucleic acids: a structure for deoxyribose nucleic acid , solvation shell , stereochemistry , molecule , biochemistry , organic chemistry
Abstract Recent experiments have presented evidence that Watson–Crick hydrogen bonds in a base pair are not absolute requirements for efficient synthesis of that pair by DNA polymerase enzymes. Here we examine quantitative steady‐state kinetic data from several published studies involving poorly hydrogen‐bonding DNA base analogues and adducts, and analyze the results in terms of solvation, 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 during 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. © 1998 John Wiley & Sons, Inc. Biopoly 48: 3–17, 1998