Structure of a DNA duplex containing a site-specific Dewar isomer: Structural influence of the 3 -T center dot G base pair of the Dewar product.

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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 G15 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 3'-T-->C mutation at this site.
Publisher
SPRINGER-VERLAG SINGAPORE PTE LTD
Issue Date
2000-05
Language
English
Article Type
Article
Keywords

ESCHERICHIA-COLI; CIS-SYN; CYCLOBUTANE DIMERS; DECAMER DUPLEX; 6-4 ADDUCT; NMR; PHOTOPRODUCTS; THYMIDYLYL(3' -> 5' )THYMIDINE; CONFORMATION; MUTATIONS

Citation

JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY, v.33, no.3, pp.268 - 275

ISSN
1225-8687
URI
http://hdl.handle.net/10203/75408
Appears in Collection
CH-Journal Papers(저널논문)
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