Efficient replication between non-hydrogen-bonded nucleoside shape analogs
DNA Replication
0301 basic medicine
Deoxyadenosines
Nucleotides
Imidazoles
Hydrogen Bonding
Nucleosides
DNA Polymerase I
Kinetics
03 medical and health sciences
Adenosine Triphosphate
Benzimidazoles
Base Pairing
Thymine
DOI:
10.1038/2925
Publication Date:
2002-07-26T08:47:57Z
AUTHORS (2)
ABSTRACT
DNA polymerase enzymes make an error only once per 10(4)-10(5) initial nucleotide insertions during DNA replication. Most currently held models of this high fidelity cite the hydrogen bonds between complementary pyrimidines and purines as a critical controlling factor. Testing this has been difficult, however, since standard molecular strategies for blocking or removing polar hydrogen-bonding groups cause changes to size and shape as well as hydrogen bonding ability. One answer to this problem is the use of nonpolar molecules that mimic the shape of natural DNA bases. Here we show that a non-hydrogen-bonding shape mimic for adenine is replicated efficiently and selectively against a nonpolar shape mimic for thymine. The results establish that hydrogen bonds in a base pair are not absolutely required for efficient nucleotide insertion. This adds support to the idea that shape complementarity may play as important a role in replication as base-base hydrogen bonds.
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