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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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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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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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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DOI: https://doi.org/10.1038/nsmb.1852
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