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Sequence-dependent mechanics of single DNA molecules

Nature Structural Biology volume 6, pages 346–349 (1999)Cite this article

Abstract

Atomic force microscope–based single-molecule force spectroscopy was employed to measure sequence-dependent mechanical properties of DNA by stretching individual DNA double strands attached between a gold surface and an AFM tip. We discovered that in λ-phage DNA the previously reported B-S transition, where 'S' represents an overstretched conformation, at 65 pN is followed by a nonequilibrium melting transition at 150 pN. During this transition the DNA is split into single strands that fully recombine upon relaxation. The sequence dependence was investigated in comparative studies with poly(dG-dC) and poly(dA-dT) DNA. Both the B-S and the melting transition occur at significantly lower forces in poly(dA-dT) compared to poly(dG-dC). We made use of the melting transition to prepare single poly(dG-dC) and poly(dA-dT) DNA strands that upon relaxation reannealed into hairpins as a result of their self-complementary sequence. The unzipping of these hairpins directly revealed the base pair–unbinding forces for G-C to be 20 ± 3 pN and for A-T to be 9 ± 3 pN.

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Figure 1: Force-induced melting transition in λ-DNA.
Figure 2: The mechanical compliance of DNA strongly depends on the specific base pairing in the double helix.
Figure 3: Direct measurement of base-pairing forces.

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References

  1. Smith, S.B., Finzi, L. & Bustamante, C. Science 258, 1122–1126 (1992).

    Article  CAS  Google Scholar 

  2. Florin, E.-L., Moy, V.T. & Gaub, H.E. Science 264, 415–417 (1994).

    Article  CAS  Google Scholar 

  3. Lee, G.U., Chris, L.A. & Colton, R.J. Science 266, 771–773 (1994).

    Article  CAS  Google Scholar 

  4. Yin, H. et al. Science 270, 1653–1657 (1995).

    Article  CAS  Google Scholar 

  5. Kasas, S. et al. Biochemistry 36, 461–468 (1997).

    Article  CAS  Google Scholar 

  6. Rief, M., Oesterhelt, F., Heymann, B. & Gaub, H.E. Science 275, 1295–1298 (1997).

    Article  CAS  Google Scholar 

  7. Li, H., Rief, M., Oesterhelt, F. & Gaub, H.E. Advanced Materials 10, 316–319 (1998).

    Article  CAS  Google Scholar 

  8. Rief, M., Gautel, M., Oesterhelt, F., Fernandez, J.M. & Gaub, H.E. Science 276, 1109–1112 (1997).

    Article  CAS  Google Scholar 

  9. Tskhovrebova, L., Trinick, J., Sleep, J.A. & Simmons, R.M. Nature 387, 308–312 (1997).

    Article  CAS  Google Scholar 

  10. Kellermayer, M.S., Smith, S.B., Granzier, H.L. & Bustamante, C. Science 276, 1112–1116 (1997).

    Article  CAS  Google Scholar 

  11. Oberhauser, A.F., Marszalek, P.E., Erickson, H.P. & Fernandez, J.M. Nature 393, 181–185 (1998).

    Article  CAS  Google Scholar 

  12. Smith, S.B., Cui, Y. & Bustamante, C. Science 271, 795–798 (1996).

    Article  CAS  Google Scholar 

  13. Cluzel, P. et al. Science 271, 792–794 (1996).

    Article  CAS  Google Scholar 

  14. Bensimon, D., Simon, A.J., Croquette, V. & Bensimon, A. Phys. Rev. Lett. 74, 4754–4757 (1995).

    Article  CAS  Google Scholar 

  15. Lebrun, A. & Lavery, R. Nucleic Acids Res. 24, 2260–2267 (1996).

    Article  CAS  Google Scholar 

  16. Konrad, M.W. & Bolonick, J.I. J. Am. Chem. Soc. 118, 10989–10994 (1996).

    Article  CAS  Google Scholar 

  17. Ahsan, A., Rudnick, J. & Bruinsma, R. Biophys. J. 74, 132–137 (1998).

    Article  CAS  Google Scholar 

  18. Essevaz-Roulet, B., Bockelmann, U. & Heslot, F. Proc. Natl. Acad. Sci. USA 94, 11935–11940 (1997).

    Article  CAS  Google Scholar 

  19. Bockelmann, U., Essevaz-Roulet, B. & Heslot, F. Phys. Rev. Lett. 79, 4489–4492 (1997).

    Article  CAS  Google Scholar 

  20. Binnig, G., Quate, C.F. & Gerber, C. Phys. Rev. Lett. 56, 930 (1986).

    Article  CAS  Google Scholar 

  21. Xodo, L.E., Manzini, G., Quadrifoglio, F., van der Marel, G.A. & van Boom, J.H. Biochemistry 27, 6321–6326 (1988).

    Article  CAS  Google Scholar 

  22. Rief, M., Fernandez, J.M. & Gaub, H.E. Phys. Rev. Lett. 81, 4764–4767 (1998).

    Article  CAS  Google Scholar 

  23. Breslauer, K.J., Frank, R., Blöcker, H. & Marky, L.A. Proc. Natl. Acad. Sci. USA 83, 3746–3750 (1986).

    Article  CAS  Google Scholar 

  24. Florin, E.L. et al. Biosens. Bioelectron. 10, 895–901 (1995).

    Article  CAS  Google Scholar 

  25. Butt, H.-J. & Jaschke, M. Nanotechnology 6, 1–7 (1995).

    Article  Google Scholar 

Download references

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Author notes

  1. Matthias Rief

    Present address: Department of Biochemistry B400, Stanford University School of Medicine, Stanford, California, 94305-5307, USA

Authors and Affiliations

  1. Lehrstuhl für Angewandte Physik, Amalienstraße 54, München, 80799, Germany

    Matthias Rief, Hauke Clausen-Schaumann & Hermann E. Gaub

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  1. Matthias Rief
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  2. Hauke Clausen-Schaumann
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  3. Hermann E. Gaub
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Correspondence to Hermann E. Gaub.

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Rief, M., Clausen-Schaumann, H. & Gaub, H. Sequence-dependent mechanics of single DNA molecules. Nat Struct Mol Biol 6, 346–349 (1999). https://doi.org/10.1038/7582

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