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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Mar 15;88(6):2312–2316. doi: 10.1073/pnas.88.6.2312

Curved DNA without A-A: experimental estimation of all 16 DNA wedge angles.

A Bolshoy 1, P McNamara 1, R E Harrington 1, E N Trifonov 1
PMCID: PMC51221  PMID: 2006170

Abstract

The principal sequence feature responsible for intrinsic DNA curvature is generally assumed to be runs of adenines. However, according to the wedge model of DNA curvature, each dinucleotide step is associated with a characteristic deflection of the local helix axis. Thus, an important test of a more general view of sequence-dependent DNA curvature is whether sequence elements other than A-A cause the DNA axis to deflect. To address this question, we have applied the wedge model to a large body of experimental data. The axial path of DNA can be described at each step by three Eulerian angles: the helical twist, the deflection angle (wedge angle), and the direction of the deflection. Circularization and gel electrophoretic mobility data on 54 synthetic DNA fragments, both from other laboratories and from our own, were used to compare the theoretical predictions of the wedge model with experiment. By minimizing misfit between calculated and observed DNA curvature, we have found that the stacks AG/CT, CG/CG, GA/TC, and GC/GC, in addition to AA/TT, have large wedge values. We have also synthesized seven sequences without AA/TT elements but with these other wedges correctly phased to cause appreciable predicted curvature. All appear curved as demonstrated by anomalous gel mobilities. The full set of 16 roll and tilt wedge angles is estimated and, together with the known 10 helical twists, these allow prediction of the general sequence-dependent trajectory of the DNA axis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barber A. M., Zhurkin V. B. CAP binding sites reveal pyrimidine-purine pattern characteristic of DNA bending. J Biomol Struct Dyn. 1990 Oct;8(2):213–232. doi: 10.1080/07391102.1990.10507803. [DOI] [PubMed] [Google Scholar]
  2. Bracco L., Kotlarz D., Kolb A., Diekmann S., Buc H. Synthetic curved DNA sequences can act as transcriptional activators in Escherichia coli. EMBO J. 1989 Dec 20;8(13):4289–4296. doi: 10.1002/j.1460-2075.1989.tb08615.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burkhoff A. M., Tullius T. D. Structural details of an adenine tract that does not cause DNA to bend. Nature. 1988 Feb 4;331(6155):455–457. doi: 10.1038/331455a0. [DOI] [PubMed] [Google Scholar]
  4. Cacchione S., De Santis P., Foti D., Palleschi A., Savino M. Periodical polydeoxynucleotides and DNA curvature. Biochemistry. 1989 Oct 31;28(22):8706–8713. doi: 10.1021/bi00448a006. [DOI] [PubMed] [Google Scholar]
  5. Calladine C. R., Drew H. R., McCall M. J. The intrinsic curvature of DNA in solution. J Mol Biol. 1988 May 5;201(1):127–137. doi: 10.1016/0022-2836(88)90444-5. [DOI] [PubMed] [Google Scholar]
  6. Cheung S., Arndt K., Lu P. Correlation of lac operator DNA imino proton exchange kinetics with its function. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3665–3669. doi: 10.1073/pnas.81.12.3665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chuprina V. P. Critical comments on the one recent DNA bending model and its fit to electrophoretic data. J Biomol Struct Dyn. 1989 Aug;7(1):35–40c. doi: 10.1080/07391102.1989.10507749. [DOI] [PubMed] [Google Scholar]
  8. Cowie A., Myers R. M. DNA sequences involved in transcriptional regulation of the mouse beta-globin promoter in murine erythroleukemia cells. Mol Cell Biol. 1988 Aug;8(8):3122–3128. doi: 10.1128/mcb.8.8.3122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Diekmann S., McLaughlin L. W. DNA curvature in native and modified EcoRI recognition sites and possible influence upon the endonuclease cleavage reaction. J Mol Biol. 1988 Aug 20;202(4):823–834. doi: 10.1016/0022-2836(88)90561-x. [DOI] [PubMed] [Google Scholar]
  10. Diekmann S. Sequence specificity of curved DNA. FEBS Lett. 1986 Jan 20;195(1-2):53–56. doi: 10.1016/0014-5793(86)80128-4. [DOI] [PubMed] [Google Scholar]
  11. Diekmann S. Temperature and salt dependence of the gel migration anomaly of curved DNA fragments. Nucleic Acids Res. 1987 Jan 12;15(1):247–265. doi: 10.1093/nar/15.1.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Diekmann S. The migration anomaly of DNA fragments in polyacrylamide gels allows the detection of small sequence-specific DNA structure variations. Electrophoresis. 1989 May-Jun;10(5-6):354–359. doi: 10.1002/elps.1150100513. [DOI] [PubMed] [Google Scholar]
  13. Dong F., Hansen J. C., van Holde K. E. DNA and protein determinants of nucleosome positioning on sea urchin 5S rRNA gene sequences in vitro. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5724–5728. doi: 10.1073/pnas.87.15.5724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fujimura F. K. Point mutation in the polyomavirus enhancer alters local DNA conformation. Nucleic Acids Res. 1988 Mar 25;16(5):1987–1997. doi: 10.1093/nar/16.5.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hagerman P. J. Sequence dependence of the curvature of DNA: a test of the phasing hypothesis. Biochemistry. 1985 Dec 3;24(25):7033–7037. doi: 10.1021/bi00346a001. [DOI] [PubMed] [Google Scholar]
  16. Hagerman P. J. Sequence dependence of the curvature of DNA: a test of the phasing hypothesis. Biochemistry. 1985 Dec 3;24(25):7033–7037. doi: 10.1021/bi00346a001. [DOI] [PubMed] [Google Scholar]
  17. Hagerman P. J. Sequence-directed curvature of DNA. Nature. 1986 May 22;321(6068):449–450. doi: 10.1038/321449a0. [DOI] [PubMed] [Google Scholar]
  18. Hagerman P. J. Sequence-directed curvature of DNA. Annu Rev Biochem. 1990;59:755–781. doi: 10.1146/annurev.bi.59.070190.003543. [DOI] [PubMed] [Google Scholar]
  19. Haran T. E., Crothers D. M. Cooperativity in A-tract structure and bending properties of composite TnAn blocks. Biochemistry. 1989 Apr 4;28(7):2763–2767. doi: 10.1021/bi00433a003. [DOI] [PubMed] [Google Scholar]
  20. Hesse J. E., Lieber M. R., Mizuuchi K., Gellert M. V(D)J recombination: a functional definition of the joining signals. Genes Dev. 1989 Jul;3(7):1053–1061. doi: 10.1101/gad.3.7.1053. [DOI] [PubMed] [Google Scholar]
  21. Husain I., Griffith J., Sancar A. Thymine dimers bend DNA. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2558–2562. doi: 10.1073/pnas.85.8.2558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kabsch W., Sander C., Trifonov E. N. The ten helical twist angles of B-DNA. Nucleic Acids Res. 1982 Feb 11;10(3):1097–1104. doi: 10.1093/nar/10.3.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Koo H. S., Crothers D. M. Calibration of DNA curvature and a unified description of sequence-directed bending. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1763–1767. doi: 10.1073/pnas.85.6.1763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Koo H. S., Drak J., Rice J. A., Crothers D. M. Determination of the extent of DNA bending by an adenine-thymine tract. Biochemistry. 1990 May 1;29(17):4227–4234. doi: 10.1021/bi00469a027. [DOI] [PubMed] [Google Scholar]
  25. Koo H. S., Wu H. M., Crothers D. M. DNA bending at adenine . thymine tracts. Nature. 1986 Apr 10;320(6062):501–506. doi: 10.1038/320501a0. [DOI] [PubMed] [Google Scholar]
  26. Leroy J. L., Charretier E., Kochoyan M., Guéron M. Evidence from base-pair kinetics for two types of adenine tract structures in solution: their relation to DNA curvature. Biochemistry. 1988 Dec 13;27(25):8894–8898. doi: 10.1021/bi00425a004. [DOI] [PubMed] [Google Scholar]
  27. Levene S. D., Crothers D. M. A computer graphics study of sequence-directed bending in DNA. J Biomol Struct Dyn. 1983 Oct;1(2):429–435. doi: 10.1080/07391102.1983.10507452. [DOI] [PubMed] [Google Scholar]
  28. Lu P., Cheung S., Arndt K. Possible molecular detent in the DNA structure at regulatory sequences. J Biomol Struct Dyn. 1983 Oct;1(2):509–521. doi: 10.1080/07391102.1983.10507458. [DOI] [PubMed] [Google Scholar]
  29. Marini J. C., Levene S. D., Crothers D. M., Englund P. T. Bent helical structure in kinetoplast DNA. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7664–7668. doi: 10.1073/pnas.79.24.7664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. McNamara P. T., Bolshoy A., Trifonov E. N., Harrington R. E. Sequence-dependent kinks induced in curved DNA. J Biomol Struct Dyn. 1990 Dec;8(3):529–538. doi: 10.1080/07391102.1990.10507827. [DOI] [PubMed] [Google Scholar]
  31. Milton D. L., Casper M. L., Wills N. M., Gesteland R. F. Guanine tracts enhance sequence directed DNA bends. Nucleic Acids Res. 1990 Feb 25;18(4):817–820. doi: 10.1093/nar/18.4.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Milton D. L., Gesteland R. F. Bends in SV40 DNA: use of mutagenesis to identify the critical bases involved. Nucleic Acids Res. 1988 May 11;16(9):3931–3949. doi: 10.1093/nar/16.9.3931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nadeau J. G., Crothers D. M. Structural basis for DNA bending. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2622–2626. doi: 10.1073/pnas.86.8.2622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rice J. A., Crothers D. M., Pinto A. L., Lippard S. J. The major adduct of the antitumor drug cis-diamminedichloroplatinum(II) with DNA bends the duplex by approximately equal to 40 degrees toward the major groove. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4158–4161. doi: 10.1073/pnas.85.12.4158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Shliakhtenko L. S., Liubchenko Iu L., Chernov B. K., Zhurkin V. B. Vliianie temperatury i ionnoi sily na élektroforeticheskuiu podvizhnost' sinteticheskikh fragmentov DNK. Mol Biol (Mosk) 1990 Jan-Feb;24(1):79–95. [PubMed] [Google Scholar]
  36. Steitz T. A. Structural studies of protein-nucleic acid interaction: the sources of sequence-specific binding. Q Rev Biophys. 1990 Aug;23(3):205–280. doi: 10.1017/s0033583500005552. [DOI] [PubMed] [Google Scholar]
  37. Trifonov E. N. Curved DNA. CRC Crit Rev Biochem. 1985;19(2):89–106. doi: 10.3109/10409238509082540. [DOI] [PubMed] [Google Scholar]
  38. Trifonov E. N. Sequence-dependent deformational anisotropy of chromatin DNA. Nucleic Acids Res. 1980 Sep 11;8(17):4041–4053. doi: 10.1093/nar/8.17.4041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Trifonov E. N., Sussman J. L. The pitch of chromatin DNA is reflected in its nucleotide sequence. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3816–3820. doi: 10.1073/pnas.77.7.3816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ulanovsky L. E., Trifonov E. N. Estimation of wedge components in curved DNA. Nature. 1987 Apr 16;326(6114):720–722. doi: 10.1038/326720a0. [DOI] [PubMed] [Google Scholar]
  41. Ulanovsky L., Bodner M., Trifonov E. N., Choder M. Curved DNA: design, synthesis, and circularization. Proc Natl Acad Sci U S A. 1986 Feb;83(4):862–866. doi: 10.1073/pnas.83.4.862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Zahn K., Blattner F. R. Direct evidence for DNA bending at the lambda replication origin. Science. 1987 Apr 24;236(4800):416–422. doi: 10.1126/science.2951850. [DOI] [PubMed] [Google Scholar]

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