BMB Reports
- Volume 33 Issue 3
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- Pages.268-275
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- 2000
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- 1976-670X(eISSN)
Structure of a DNA Duplex Containing a Site-Specific Dewar Isomer: Structural Influence of the 3'-T.G base pair of the Dewar product.
- Lee, Joon-Hwa (Department of Chemistry and School of Molecular Science, Korea Advanced Institute of Science and Technology) ;
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Choi, Byong-Seok
(Department of Chemistry and School of Molecular Science, Korea Advanced Institute of Science and Technology)
- Received : 2000.03.03
- Accepted : 2000.04.18
- Published : 2000.05.31
Abstract
In contrast to the pyrimidine (6-4)pyrimidone photoproduct [(6-4) adduct], its Dewar valence isomer (Dewar product) is low mutagenic and produces a broad range of mutations with a 42 % replicating error frequency. In order to determine the origin of the mutagenic property of the Dewar product, we used experimental NMR restraints and molecular dynamics to determine the solution structure of a Dewar·lesion DNA decamer duplex, which contains a mismatched base pair between the 3'-T residue and an opposed G residue. The 3'-T of the Dewar lesion forms stable hydrogen bonds with the opposite G residue. The helical bending and unwinding angles of the DW/GA duplex, however, are much higher than those of the DW/AA duplex. The stable hydrogen bonding of the G 15 residue does not increase the thermal stability of the overall helix. It also does not restore the distorted backbone conformation of the DNA helix that is caused by the forming of a Dewar lesion. These structural features implicate that no thermal stability, or conformational benefits of G over A opposite the 3'-T of the Dewar lesion, facilitate the preferential incorporation of an A. This is in accordance with the A rule during translesion replication and leads to the low frequent