1. Dynamics and energetics of the base flipping conformation studied with base pair-mimic nucleosides.
- Author
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Nakano S, Oka H, Uotani Y, Uenishi K, Fujii M, and Sugimoto N
- Subjects
- Base Sequence, Binding Sites, Computer Simulation, DNA chemistry, DNA genetics, DNA metabolism, DNA Repair, Deoxyadenosines chemistry, Deoxyadenosines genetics, Deoxyadenosines metabolism, Deoxycytidine chemistry, Deoxycytidine genetics, Deoxycytidine metabolism, Hydrolysis, Nucleosides genetics, RNA chemistry, RNA genetics, RNA metabolism, Thermodynamics, Base Pairing, Molecular Mimicry, Nucleic Acid Conformation, Nucleosides chemistry, Nucleosides metabolism
- Abstract
A base flipping conformation is found in many biological processes, including DNA repair and DNA and RNA modification processes. To investigate the dynamics and energetics of this unusual conformation in a double helix, base flipping induced by the base pair analogues of deoxyadenosine and deoxycytidine derivatives tethering a phenyl or naphthyl group was investigated. DNA strands bearing the base pair analogues stabilized the base flipping conformation of a complementary RNA, resulting in a site-specific hydrolysis by specific base catalysis. Measurements of the hydrolysis rate and the thermal stability of DNA/RNA duplexes suggested an unconstrained flexibility of the flipped-out ribonucleotide. As established in the base flipping by DNA repair and DNA and RNA modification enzymes, the results suggested that base flipping occurred in competition with base pair formation. In addition, the deoxycytidine derivatives discriminated G from I (inosine), with respect to the base pair interaction energy, as observed for a damaged base or a weakened base pair search by DNA repair proteins. The base pair mimic nucleosides would be useful for investigating the base flipping conformation under the equilibrium with base pairing.
- Published
- 2009
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