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KlenTaq polymerase replicates unnatural base pairs by inducing a Watson-Crick geometry

Nature Chemical Biology volume 8, pages 612614 (2012) | Download Citation

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Abstract

Many candidate unnatural DNA base pairs have been developed, but some of the best-replicated pairs adopt intercalated structures in free DNA that are difficult to reconcile with known mechanisms of polymerase recognition. Here we present crystal structures of KlenTaq DNA polymerase at different stages of replication for one such pair, dNaM-d5SICS, and show that efficient replication results from the polymerase itself, inducing the required natural-like structure.

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  • 06 June 2012

    In the version of this article initially published online, the fourth author was mistakenly credited with equal contribution to that of the first two authors. The error has been corrected in the print, PDF and HTML versions of this article.

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Acknowledgements

We thank the beamline staff of the Swiss Light Source at the Paul Scherrer Institute for their assistance during data collection. This work was supported by the Konstanz Research School Chemical Biology (to K.B.) and the US National Institutes of Health (GM060005 to F.E.R.).

Author information

Author notes

    • Karin Betz
    •  & Denis A Malyshev

    These authors contributed equally to this work.

Affiliations

  1. Department of Chemistry, Universität Konstanz, Konstanz, Germany.

    • Karin Betz
    •  & Andreas Marx
  2. Konstanz Research School–Chemical Biology, Universität Konstanz, Konstanz, Germany.

    • Karin Betz
    • , Wolfram Welte
    •  & Kay Diederichs
  3. Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA.

    • Denis A Malyshev
    • , Thomas Lavergne
    •  & Floyd E Romesberg
  4. Department of Biology, Universität Konstanz, Konstanz, Germany.

    • Wolfram Welte
    •  & Kay Diederichs
  5. Department of Chemistry and Biochemistry, University of San Diego, San Diego, California, USA.

    • Tammy J Dwyer
  6. The Center for Protein and Nucleic Acid Research, The Scripps Research Institute, La Jolla, California, USA.

    • Phillip Ordoukhanian

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Contributions

K.B., D.A.M., T.L., F.E.R. and A.M. conceived of the project, designed the experiments and analyzed the data. K.B., D.A.M., T.L. and P.O. performed chemical synthesis. K.B., W.W. and K.D. performed crystallography studies. T.J.D. performed the NMR experiments, and D.A.M. and T.J.D. performed modeling studies. K.B., D.A.M., A.M. and F.E.R. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Floyd E Romesberg or Andreas Marx.

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DOI

https://doi.org/10.1038/nchembio.966

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