Skip to main content
SpringerLink
Log in

DNA-catalyzed sequence-specific hydrolysis of DNA

  • Brief Communication
  • Published:

From Nature Chemical Biology

View current issue Submit your manuscript

Abstract

Deoxyribozymes (DNA catalysts) have been reported for cleavage of RNA phosphodiester linkages, but cleaving peptide or DNA phosphodiester linkages is much more challenging. Using in vitro selection, here we identified deoxyribozymes that sequence-specifically hydrolyze DNA with multiple turnover and with a rate enhancement of 108 (possibly as high as 1014). The new DNA catalysts require both Mn2+ and Zn2+, which is noteworthy because many natural DNA nucleases are bimetallic protein enzymes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1: In vitro selection of deoxyribozymes that cleave a substrate with both amide and DNA phosphodiester linkages.
Figure 2: Hydrolysis of DNA phosphodiester bonds by the new deoxyribozymes.

Similar content being viewed by others

References

  1. Breaker, R.R. & Joyce, G.F. Chem. Biol. 1, 223–229 (1994).

    Article  CAS  Google Scholar 

  2. Silverman, S.K. Chem. Commun. (Camb.) 3467–3485 (2008).

  3. Silverman, S.K. Nucleic Acids Res. 33, 6151–6163 (2005).

    Article  CAS  Google Scholar 

  4. Santoro, S.W. & Joyce, G.F. Proc. Natl. Acad. Sci. USA 94, 4262–4266 (1997).

    Article  CAS  Google Scholar 

  5. Schlosser, K., Gu, J., Lam, J.C. & Li, Y. Nucleic Acids Res. 36, 4768–4777 (2008).

    Article  CAS  Google Scholar 

  6. Carmi, N. & Breaker, R.R. Bioorg. Med. Chem. 9, 2589–2600 (2001).

    Article  CAS  Google Scholar 

  7. Liu, X. et al. Chem. Commun. (Camb.) 380–382 (2008).

  8. Radzicka, A. & Wolfenden, R. J. Am. Chem. Soc. 118, 6105–6109 (1996).

    Article  CAS  Google Scholar 

  9. Radzicka, A. & Wolfenden, R. Science 267, 90–93 (1995).

    Article  CAS  Google Scholar 

  10. Schroeder, G.K., Lad, C., Wyman, P., Williams, N.H. & Wolfenden, R. Proc. Natl. Acad. Sci. USA 103, 4052–4055 (2006).

    Article  CAS  Google Scholar 

  11. Williams, N.H., Takasaki, B., Wall, M. & Chin, J. Acc. Chem. Res. 32, 485–493 (1999).

    Article  CAS  Google Scholar 

  12. Robertson, D.L. & Joyce, G.F. Nature 344, 467–468 (1990).

    Article  CAS  Google Scholar 

  13. Mancin, F., Scrimin, P., Tecilla, P. & Tonellato, U. Chem. Commun. (Camb.) 2540–2548 (2005).

  14. Mancin, F. & Tecilla, P. New J. Chem. 31, 800–817 (2007).

    Article  CAS  Google Scholar 

  15. Dai, X., De Mesmaeker, A. & Joyce, G.F. Science 267, 237–240 (1995).

    Article  CAS  Google Scholar 

  16. Flynn-Charlebois, A. et al. J. Am. Chem. Soc. 125, 2444–2454 (2003).

    Article  CAS  Google Scholar 

  17. Wada, T., Moriguchi, T. & Sekine, M. J. Am. Chem. Soc. 116, 9901–9911 (1994).

    Article  CAS  Google Scholar 

  18. Kost, D.M., Gerdt, J.P., Pradeepkumar, P.I. & Silverman, S.K. Org. Biomol. Chem. 6, 4391–4398 (2008).

    Article  CAS  Google Scholar 

  19. Hoadley, K.A., Purtha, W.E., Wolf, A.C., Flynn-Charlebois, A. & Silverman, S.K. Biochemistry 44, 9217–9231 (2005).

    Article  CAS  Google Scholar 

  20. Silverman, S.K. in Wiley Encyclopedia of Chemical Biology (ed. Begley, T.P.) (John Wiley and Sons, Hoboken, New Jersey, 2009).

    Google Scholar 

  21. Shell, T.A., Glass, J.E., Mackey, M.A., Layman, K.A. & Mohler, D.L. Inorg. Chem. 46, 8120–8122 (2007).

    Article  CAS  Google Scholar 

  22. Pradeepkumar, P.I., Höbartner, C., Baum, D.A. & Silverman, S.K. Angew. Chem. Int. Ed. 47, 1753–1757 (2008).

    Article  CAS  Google Scholar 

  23. Wilcox, D.E. Chem. Rev. 96, 2435–2458 (1996).

    Article  CAS  Google Scholar 

  24. Shan, S.O., Kravchuk, A.V., Piccirilli, J.A. & Herschlag, D. Biochemistry 40, 5161–5171 (2001).

    Article  CAS  Google Scholar 

  25. Kim, Y.G., Cha, J. & Chandrasegaran, S. Proc. Natl. Acad. Sci. USA 93, 1156–1160 (1996).

    Article  CAS  Google Scholar 

  26. Komiyama, M., Aiba, Y., Yamamoto, Y. & Sumaoka, J. Nat. Protoc. 3, 655–662 (2008).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the US National Institutes of Health (GM065966), the US Defense Threat Reduction Agency (BRBAA08-l-2-0001) and the David and Lucile Packard Foundation. A.S. was partially supported by the US National Institutes of Health (National Institute of General Medical Sciences) under the Ruth L. Kirschstein National Research Service Award T32 GM070421. We thank D. Ghosh and P. Bevilacqua (Pennsylvania State University) for independently verifying the cleavage activity of the 10MD5 deoxyribozyme with an all-DNA substrate. We thank L.A. Furgerson Ihnken and W. van der Donk for expert assistance with and access to the ESI mass spectrometer for the 18O-water experiment.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA

    Madhavaiah Chandra, Amit Sachdeva & Scott K Silverman

Authors
  1. Madhavaiah Chandra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amit Sachdeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Scott K Silverman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.C. performed in vitro selections using substrates synthesized by A.S. M.C. and A.S. characterized the deoxyribozymes. S.K.S. conceived the project, assisted M.C. and A.S. with analysis of experimental data and wrote the manuscript with input from M.C. and A.S.

Corresponding author

Correspondence to Scott K Silverman.

Supplementary information

Supplementary Text and Figures

Supplementary Methods (PDF 5077 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chandra, M., Sachdeva, A. & Silverman, S. DNA-catalyzed sequence-specific hydrolysis of DNA. Nat Chem Biol 5, 718–720 (2009). https://doi.org/10.1038/nchembio.201

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.201

  • Springer Nature America, Inc.

This article is cited by

Search

Navigation