Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1998 Sep 15;26(18):4274–4279. doi: 10.1093/nar/26.18.4274

Unconventional helical phasing of repetitive DNA motifs reveals their relative bending contributions.

M Dlakic 1, R E Harrington 1
PMCID: PMC147818  PMID: 9722649

Abstract

A novel, multiple DNA phasing analysis is described in which three sequence motifs associated with bent DNA are clustered together in oligomers of identical base composition, but with different phasing relationships of these motifs to each other. Synthetic oligonucleotides containing different combinations of AAAAA(A), GGGCCC and GAGAG sequence motifs were ligated and analyzed by gel mobility and cyclization experiments to determine their global curvature. These assays were used to obtain relative bending contributions of the analyzed sequence motifs. The experimental results also provide a rigorous test of predictive models for DNA bending. We report, using molecular modeling, that none of the most widely used dinucleotide (nearest neighbor) models can accurately describe the conformational properties of these DNA sequences and that more complex models, at least at the trinucleotide level, are required.

Full Text

The Full Text of this article is available as a PDF (120.5 KB).

Selected References

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

  1. Bansal M., Bhattacharyya D., Ravi B. NUPARM and NUCGEN: software for analysis and generation of sequence dependent nucleic acid structures. Comput Appl Biosci. 1995 Jun;11(3):281–287. doi: 10.1093/bioinformatics/11.3.281. [DOI] [PubMed] [Google Scholar]
  2. Bolshoy A., McNamara P., Harrington R. E., Trifonov E. N. Curved DNA without A-A: experimental estimation of all 16 DNA wedge angles. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2312–2316. doi: 10.1073/pnas.88.6.2312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brukner I., Susic S., Dlakic M., Savic A., Pongor S. Physiological concentration of magnesium ions induces a strong macroscopic curvature in GGGCCC-containing DNA. J Mol Biol. 1994 Feb 11;236(1):26–32. doi: 10.1006/jmbi.1994.1115. [DOI] [PubMed] [Google Scholar]
  4. Brukner I., Sánchez R., Suck D., Pongor S. Sequence-dependent bending propensity of DNA as revealed by DNase I: parameters for trinucleotides. EMBO J. 1995 Apr 18;14(8):1812–1818. doi: 10.1002/j.1460-2075.1995.tb07169.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brukner I., Sánchez R., Suck D., Pongor S. Trinucleotide models for DNA bending propensity: comparison of models based on DNaseI digestion and nucleosome packaging data. J Biomol Struct Dyn. 1995 Oct;13(2):309–317. doi: 10.1080/07391102.1995.10508842. [DOI] [PubMed] [Google Scholar]
  6. Buckin V. A., Kankiya B. I., Bulichov N. V., Lebedev A. V., Gukovsky IYa, Chuprina V. P., Sarvazyan A. P., Williams A. R. Measurement of anomalously high hydration of (dA)n.(dT)n double helices in dilute solution. Nature. 1989 Jul 27;340(6231):321–322. doi: 10.1038/340321a0. [DOI] [PubMed] [Google Scholar]
  7. Chan S. S., Breslauer K. J., Hogan M. E., Kessler D. J., Austin R. H., Ojemann J., Passner J. M., Wiles N. C. Physical studies of DNA premelting equilibria in duplexes with and without homo dA.dT tracts: correlations with DNA bending. Biochemistry. 1990 Jul 3;29(26):6161–6171. doi: 10.1021/bi00478a008. [DOI] [PubMed] [Google Scholar]
  8. De Santis P., Palleschi A., Savino M., Scipioni A. Validity of the nearest-neighbor approximation in the evaluation of the electrophoretic manifestations of DNA curvature. Biochemistry. 1990 Oct 2;29(39):9269–9273. doi: 10.1021/bi00491a023. [DOI] [PubMed] [Google Scholar]
  9. DiGabriele A. D., Steitz T. A. A DNA dodecamer containing an adenine tract crystallizes in a unique lattice and exhibits a new bend. J Mol Biol. 1993 Jun 20;231(4):1024–1039. doi: 10.1006/jmbi.1993.1349. [DOI] [PubMed] [Google Scholar]
  10. Dickerson R. E. DNA bending: the prevalence of kinkiness and the virtues of normality. Nucleic Acids Res. 1998 Apr 15;26(8):1906–1926. doi: 10.1093/nar/26.8.1906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dickerson R. E., Goodsell D. S., Neidle S. "...the tyranny of the lattice...". Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3579–3583. doi: 10.1073/pnas.91.9.3579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dickerson R. E., Goodsell D., Kopka M. L. MPD and DNA bending in crystals and in solution. J Mol Biol. 1996 Feb 16;256(1):108–125. doi: 10.1006/jmbi.1996.0071. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Dlakic M., Harrington R. E. Bending and torsional flexibility of G/C-rich sequences as determined by cyclization assays. J Biol Chem. 1995 Dec 15;270(50):29945–29952. doi: 10.1074/jbc.270.50.29945. [DOI] [PubMed] [Google Scholar]
  15. Dlakic M., Harrington R. E. DIAMOD: display and modeling of DNA bending. Bioinformatics. 1998;14(4):326–331. doi: 10.1093/bioinformatics/14.4.326. [DOI] [PubMed] [Google Scholar]
  16. Dlakic M., Park K., Griffith J. D., Harvey S. C., Harrington R. E. The organic crystallizing agent 2-methyl-2,4-pentanediol reduces DNA curvature by means of structural changes in A-tracts. J Biol Chem. 1996 Jul 26;271(30):17911–17919. doi: 10.1074/jbc.271.30.17911. [DOI] [PubMed] [Google Scholar]
  17. Dlakić M., Harrington R. E. The effects of sequence context on DNA curvature. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3847–3852. doi: 10.1073/pnas.93.9.3847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Drew H. R., Travers A. A. DNA structural variations in the E. coli tyrT promoter. Cell. 1984 Jun;37(2):491–502. doi: 10.1016/0092-8674(84)90379-9. [DOI] [PubMed] [Google Scholar]
  19. Gabrielian A., Pongor S. Correlation of intrinsic DNA curvature with DNA property periodicity. FEBS Lett. 1996 Sep 9;393(1):65–68. doi: 10.1016/0014-5793(96)00855-1. [DOI] [PubMed] [Google Scholar]
  20. Ganunis R. M., Guo H., Tullius T. D. Effect of the crystallizing agent 2-methyl-2,4-pentanediol on the structure of adenine tract DNA in solution. Biochemistry. 1996 Oct 29;35(43):13729–13732. doi: 10.1021/bi961880q. [DOI] [PubMed] [Google Scholar]
  21. Goodsell D. S., Dickerson R. E. Bending and curvature calculations in B-DNA. Nucleic Acids Res. 1994 Dec 11;22(24):5497–5503. doi: 10.1093/nar/22.24.5497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Goodsell D. S., Kopka M. L., Cascio D., Dickerson R. E. Crystal structure of CATGGCCATG and its implications for A-tract bending models. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2930–2934. doi: 10.1073/pnas.90.7.2930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gorin A. A., Zhurkin V. B., Olson W. K. B-DNA twisting correlates with base-pair morphology. J Mol Biol. 1995 Mar 17;247(1):34–48. doi: 10.1006/jmbi.1994.0120. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Hagerman P. J. Sequence-directed curvature of DNA. Nature. 1986 May 22;321(6068):449–450. doi: 10.1038/321449a0. [DOI] [PubMed] [Google Scholar]
  26. Han G. W., Kopka M. L., Cascio D., Grzeskowiak K., Dickerson R. E. Structure of a DNA analog of the primer for HIV-1 RT second strand synthesis. J Mol Biol. 1997 Jun 27;269(5):811–826. doi: 10.1006/jmbi.1997.1085. [DOI] [PubMed] [Google Scholar]
  27. Han W., Dlakic M., Zhu Y. J., Lindsay S. M., Harrington R. E. Strained DNA is kinked by low concentrations of Zn2+. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10565–10570. doi: 10.1073/pnas.94.20.10565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Haran T. E., Kahn J. D., Crothers D. M. Sequence elements responsible for DNA curvature. J Mol Biol. 1994 Nov 25;244(2):135–143. doi: 10.1006/jmbi.1994.1713. [DOI] [PubMed] [Google Scholar]
  29. Harvey S. C., Dlakic M., Griffith J., Harrington R., Park K., Sprous D., Zacharias W. What is the basis of sequence-directed curvature in DNAs containing A tracts? J Biomol Struct Dyn. 1995 Oct;13(2):301–307. doi: 10.1080/07391102.1995.10508841. [DOI] [PubMed] [Google Scholar]
  30. Herrera J. E., Chaires J. B. A premelting conformational transition in poly(dA)-Poly(dT) coupled to daunomycin binding. Biochemistry. 1989 Mar 7;28(5):1993–2000. doi: 10.1021/bi00431a006. [DOI] [PubMed] [Google Scholar]
  31. Kahn J. D., Yun E., Crothers D. M. Detection of localized DNA flexibility. Nature. 1994 Mar 10;368(6467):163–166. doi: 10.1038/368163a0. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. 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]
  35. Park Y. W., Breslauer K. J. A spectroscopic and calorimetric study of the melting behaviors of a "bent" and a "normal" DNA duplex: [d(GA4T4C)]2 versus [d(GT4A4C)]2. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1551–1555. doi: 10.1073/pnas.88.4.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Satchwell S. C., Drew H. R., Travers A. A. Sequence periodicities in chicken nucleosome core DNA. J Mol Biol. 1986 Oct 20;191(4):659–675. doi: 10.1016/0022-2836(86)90452-3. [DOI] [PubMed] [Google Scholar]
  37. Sprous D., Zacharias W., Wood Z. A., Harvey S. C. Dehydrating agents sharply reduce curvature in DNAs containing A tracts. Nucleic Acids Res. 1995 May 25;23(10):1816–1821. doi: 10.1093/nar/23.10.1816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. 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]
  40. Ulyanov N. B., James T. L. Statistical analysis of DNA duplex structural features. Methods Enzymol. 1995;261:90–120. doi: 10.1016/s0076-6879(95)61006-5. [DOI] [PubMed] [Google Scholar]
  41. Wu H. M., Crothers D. M. The locus of sequence-directed and protein-induced DNA bending. Nature. 1984 Apr 5;308(5959):509–513. doi: 10.1038/308509a0. [DOI] [PubMed] [Google Scholar]
  42. Zhurkin V. B., Lysov Y. P., Ivanov V. I. Anisotropic flexibility of DNA and the nucleosomal structure. Nucleic Acids Res. 1979 Mar;6(3):1081–1096. doi: 10.1093/nar/6.3.1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Zinkel S. S., Crothers D. M. DNA bend direction by phase sensitive detection. Nature. 1987 Jul 9;328(6126):178–181. doi: 10.1038/328178a0. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES