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Structure of a DNA base-excision product resembling a cisplatin inter-strand adduct

Nature Structural Biology volume 5, pages 697–701 (1998)Cite this article

Abstract

Base-excision of a self-complementary oligonucleotide with central G:T mismatches by the G:T/U-specific mismatch DNA glycosylase (MUG), generates an unusual DNA structure which is remarkably similar in conformation to an interstrand DNA adduct of the anti-tumor drug cis -diamminedichloroplatinum. The abasic sugars generated by excision of the mismatched thymines are extruded from the double-helix, and the 'widowed' deoxyguanosines rotate so that their N7 and O6 groups protrude into the minor groove of the duplex and restack in an interleaved intercalative geometry, generating a kink in the helix axis.

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Figure 1: Structure of MUG–DNA base-excision product complex.
Figure 2: Rotation and restacking of the widowed deoxyguanosines and extrusion of the abasic sugars.
Figure 3: Comparison with interstrand cisplatin adduct.

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Acknowledgements

We thank our colleagues for assistance with data collection and the Ludwig Institute for Cancer Research and the CLRC Daresbury Laboratory for provision of X-ray diffraction facilities. We are particularly grateful to P. Hopkins and S. Thor Sigurdsson for making the coordinates of the cisplatin adduct available to us. This work was supported by the Cancer Research Campaign, as well as by the Schweizerische Krebsliga (J.J.) and the Julius Müller Stiftung (J.J.).

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Author notes

  1. Renos Savva

    Present address: Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College London, Malet Street, London, WC1E 7HX, UK

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University College London, Gower Street, London, WC1E 6BT, UK

    Tracey E. Barrett & Renos Savva

  2. Department of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK

    Tom Barlow & Tom Brown

  3. Institute of Medical Radiobiology, August Forel-Strasse 7, Zürich, 8029, Switzerland

    Josef Jiricny

  4. Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College London, Malet Street, London, WC1E 7HX, UK

    Laurence H. Pearl

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Correspondence to Laurence H. Pearl.

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Barrett, T., Savva, R., Barlow, T. et al. Structure of a DNA base-excision product resembling a cisplatin inter-strand adduct. Nat Struct Mol Biol 5, 697–701 (1998). https://doi.org/10.1038/1394

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