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Mutagenic conformation of 8-oxo-7,8-dihydro-2′-dGTP in the confines of a DNA polymerase active site

Nature Structural & Molecular Biology volume 17, pages 889–890 (2010)Cite this article

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Abstract

The major product of oxidative base damage is 8-oxo-7,8-dihydro-2′-deoxyguanine (8odG). The coding potential of this lesion is modulated by its glycosidic torsion angle that controls whether its Watson-Crick or Hoogsteen edge is used for base pairing. The 2.0-Å structure of DNA polymerase (pol) β bound with 8odGTP opposite template adenine indicates that the modified nucleotide assumes the mutagenic syn conformation and that the nonmutagenic anti conformation would be incompatible with efficient DNA synthesis.

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Figure 1: Syn conformation of 8odGTP paired with adenine.
Figure 2: Structural features that discourage insertion of 8odGTP.

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Acknowledgements

This research was supported by Research Project Number Z01-ES050158 in the Intramural Research Program of the US National Institutes of Health, US National Institute of Environmental Health Sciences and was in association with the US National Institutes of Health Grant 1U19CA105010.

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Authors and Affiliations

  1. Laboratory of Structural Biology, National Institute of Environmental Health Sciences, US National Institutes of Health, Research Triangle Park, North Carolina, USA

    Vinod K Batra, William A Beard, Esther W Hou, Lars C Pedersen, Rajendra Prasad & Samuel H Wilson

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  1. Vinod K Batra
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  2. William A Beard
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  3. Esther W Hou
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  4. Lars C Pedersen
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  5. Rajendra Prasad
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  6. Samuel H Wilson
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Contributions

E.W.H. and R.P. expressed and purified protein; L.C.P. contributed to structure refinement; V.K.B. prepared, crystallized and solved the structure of the 8odGTP–dA pol β complex; V.K.B., W.A.B. and S.H.W. analyzed data and wrote the manuscript.

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Correspondence to Samuel H Wilson.

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The authors declare no competing financial interests.

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Supplementary Figures 1–5, Supplementary Tables 1–3 and Supplementary Methods (PDF 3685 kb)

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Batra, V., Beard, W., Hou, E. et al. Mutagenic conformation of 8-oxo-7,8-dihydro-2′-dGTP in the confines of a DNA polymerase active site. Nat Struct Mol Biol 17, 889–890 (2010). https://doi.org/10.1038/nsmb.1852

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