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

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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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Figure 1: KlenTaq polymerase induces the dNaM-d5SICS unnatural base pair to adopt a natural, Watson-Crick–like structure.
Figure 2: Unnatural base pair formation induces conformational transitions of KlenTaq and the formation of a natural-like ternary complex.

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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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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.).

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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.

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Correspondence to Floyd E Romesberg or Andreas Marx.

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The authors declare no competing financial interests.

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Betz, K., Malyshev, D., Lavergne, T. et al. KlenTaq polymerase replicates unnatural base pairs by inducing a Watson-Crick geometry. Nat Chem Biol 8, 612–614 (2012).

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