Efficient replication between non-hydrogen-bonded nucleoside shape analogs

• DOI: 10.1038/2925
• Publication Date: 2002-07-26T08:47:57Z
• Authors: Juan C. Morales; Eric T. Kool
• Keywords: 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

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.