Skip to main content
Biophysical Journal logoLink to Biophysical Journal
. 1998 Feb;74(2 Pt 1):773–779. doi: 10.1016/S0006-3495(98)74002-0

Looping dynamics of linear DNA molecules and the effect of DNA curvature: a study by Brownian dynamics simulation.

H Merlitz 1, K Rippe 1, K V Klenin 1, J Langowski 1
PMCID: PMC1302558  PMID: 9533690

Abstract

A Brownian dynamics (BD) model described in the accompanying paper (Klenin, K., H. Merlitz, and J. Langowski. 1998. A Brownian dynamics program for the simulation of linear and circular DNA, and other wormlike chain polyelectrolytes. Biophys. J. 74:000-000) has been used for computing the end-to-end distance distribution function, the cyclization probability, and the cyclization kinetics of linear DNA fragments between 120 and 470 basepairs with optional insertion of DNA bends. Protein-mediated DNA loop formation was modeled by varying the reaction distance for cyclization between 0 and 10 nm. The low cyclization probability of DNA fragments shorter than the Kuhn length (300 bp) is enhanced by several orders of magnitude when the cyclization is mediated by a protein bridge of 10 nm diameter, and/or when the DNA is bent. From the BD trajectories, end-to-end collision frequencies were computed. Typical rates for loop formation of linear DNAs are 1.3 x 10(3) s(-1) (235 bp) and 4.8 x 10(2) s(-1) (470 bp), while the insertion of a 120 degree bend in the center increases this rate to 3.0 x 10(4) s(-1) (235 bp) and 5.5 x 10(3) s(-1) (470 bp), respectively. The duration of each encounter is between 0.05 and 0.5 micros for these DNAs. The results are discussed in the context of the interaction of transcription activator proteins.

Full Text

The Full Text of this article is available as a PDF (87.4 KB).

Selected References

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

  1. Affolter M., Percival-Smith A., Müller M., Leupin W., Gehring W. J. DNA binding properties of the purified Antennapedia homeodomain. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4093–4097. doi: 10.1073/pnas.87.11.4093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beachy P. A., Varkey J., Young K. E., von Kessler D. P., Sun B. I., Ekker S. C. Cooperative binding of an Ultrabithorax homeodomain protein to nearby and distant DNA sites. Mol Cell Biol. 1993 Nov;13(11):6941–6956. doi: 10.1128/mcb.13.11.6941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bednar J., Furrer P., Stasiak A., Dubochet J., Egelman E. H., Bates A. D. The twist, writhe and overall shape of supercoiled DNA change during counterion-induced transition from a loosely to a tightly interwound superhelix. Possible implications for DNA structure in vivo. J Mol Biol. 1994 Jan 21;235(3):825–847. doi: 10.1006/jmbi.1994.1042. [DOI] [PubMed] [Google Scholar]
  4. Bellomy G. R., Mossing M. C., Record M. T., Jr Physical properties of DNA in vivo as probed by the length dependence of the lac operator looping process. Biochemistry. 1988 May 31;27(11):3900–3906. doi: 10.1021/bi00411a002. [DOI] [PubMed] [Google Scholar]
  5. Bellomy G. R., Record M. T., Jr Stable DNA loops in vivo and in vitro: roles in gene regulation at a distance and in biophysical characterization of DNA. Prog Nucleic Acid Res Mol Biol. 1990;39:81–128. doi: 10.1016/s0079-6603(08)60624-8. [DOI] [PubMed] [Google Scholar]
  6. Borowiec J. A., Zhang L., Sasse-Dwight S., Gralla J. D. DNA supercoiling promotes formation of a bent repression loop in lac DNA. J Mol Biol. 1987 Jul 5;196(1):101–111. doi: 10.1016/0022-2836(87)90513-4. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Carlsson B., Häggblad J. Quantitative determination of DNA-binding parameters for the human estrogen receptor in a solid-phase, nonseparation assay. Anal Biochem. 1995 Dec 10;232(2):172–179. doi: 10.1006/abio.1995.0004. [DOI] [PubMed] [Google Scholar]
  9. Carmona M., Magasanik B. Activation of transcription at sigma 54-dependent promoters on linear templates requires intrinsic or induced bending of the DNA. J Mol Biol. 1996 Aug 23;261(3):348–356. doi: 10.1006/jmbi.1996.0468. [DOI] [PubMed] [Google Scholar]
  10. Chirico G., Langowski J. Brownian dynamics simulations of supercoiled DNA with bent sequences. Biophys J. 1996 Aug;71(2):955–971. doi: 10.1016/S0006-3495(96)79299-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ehrlich L., Münkel C., Chirico G., Langowski J. A Brownian dynamics model for the chromatin fiber. Comput Appl Biosci. 1997 Jun;13(3):271–279. doi: 10.1093/bioinformatics/13.3.271. [DOI] [PubMed] [Google Scholar]
  12. Frappier L., Goldsmith K., Bendell L. Stabilization of the EBNA1 protein on the Epstein-Barr virus latent origin of DNA replication by a DNA looping mechanism. J Biol Chem. 1994 Jan 14;269(2):1057–1062. [PubMed] [Google Scholar]
  13. Frappier L., O'Donnell M. Epstein-Barr nuclear antigen 1 mediates a DNA loop within the latent replication origin of Epstein-Barr virus. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10875–10879. doi: 10.1073/pnas.88.23.10875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gebe J. A., Allison S. A., Clendenning J. B., Schurr J. M. Monte Carlo simulations of supercoiling free energies for unknotted and trefoil knotted DNAs. Biophys J. 1995 Feb;68(2):619–633. doi: 10.1016/S0006-3495(95)80223-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gebe J. A., Schurr J. M. Thermodynamics of the first transition in writhe of a small circular DNA by Monte Carlo simulation. Biopolymers. 1996 Apr;38(4):493–503. doi: 10.1002/(SICI)1097-0282(199604)38:4%3C493::AID-BIP5%3E3.0.CO;2-O. [DOI] [PubMed] [Google Scholar]
  16. Hagerman P. J. Flexibility of DNA. Annu Rev Biophys Biophys Chem. 1988;17:265–286. doi: 10.1146/annurev.bb.17.060188.001405. [DOI] [PubMed] [Google Scholar]
  17. Hagerman P. J., Ramadevi V. A. Application of the method of phage T4 DNA ligase-catalyzed ring-closure to the study of DNA structure. I. Computational analysis. J Mol Biol. 1990 Mar 20;212(2):351–362. doi: 10.1016/0022-2836(90)90130-E. [DOI] [PubMed] [Google Scholar]
  18. Haykinson M. J., Johnson R. C. DNA looping and the helical repeat in vitro and in vivo: effect of HU protein and enhancer location on Hin invertasome assembly. EMBO J. 1993 Jun;12(6):2503–2512. doi: 10.1002/j.1460-2075.1993.tb05905.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hoopes B. C., LeBlanc J. F., Hawley D. K. Kinetic analysis of yeast TFIID-TATA box complex formation suggests a multi-step pathway. J Biol Chem. 1992 Jun 5;267(16):11539–11547. [PubMed] [Google Scholar]
  20. Kim J. L., Nikolov D. B., Burley S. K. Co-crystal structure of TBP recognizing the minor groove of a TATA element. Nature. 1993 Oct 7;365(6446):520–527. doi: 10.1038/365520a0. [DOI] [PubMed] [Google Scholar]
  21. Kim Y., Geiger J. H., Hahn S., Sigler P. B. Crystal structure of a yeast TBP/TATA-box complex. Nature. 1993 Oct 7;365(6446):512–520. doi: 10.1038/365512a0. [DOI] [PubMed] [Google Scholar]
  22. Klenin K. V., Frank-Kamenetskii M. D., Langowski J. Modulation of intramolecular interactions in superhelical DNA by curved sequences: a Monte Carlo simulation study. Biophys J. 1995 Jan;68(1):81–88. doi: 10.1016/S0006-3495(95)80161-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Klenin K. V., Vologodskii A. V., Anshelevich V. V., Dykhne A. M., Frank-Kamenetskii M. D. Computer simulation of DNA supercoiling. J Mol Biol. 1991 Feb 5;217(3):413–419. doi: 10.1016/0022-2836(91)90745-r. [DOI] [PubMed] [Google Scholar]
  24. Kremer W., Klenin K., Diekmann S., Langowski J. DNA curvature influences the internal motions of supercoiled DNA. EMBO J. 1993 Nov;12(11):4407–4412. doi: 10.1002/j.1460-2075.1993.tb06125.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Krämer H., Niemöller M., Amouyal M., Revet B., von Wilcken-Bergmann B., Müller-Hill B. lac repressor forms loops with linear DNA carrying two suitably spaced lac operators. EMBO J. 1987 May;6(5):1481–1491. doi: 10.1002/j.1460-2075.1987.tb02390.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Langowski J., Olson W. K., Pedersen S. C., Tobias I., Westcott T. P., Yang Y. DNA supercoiling, localized bending and thermal fluctuations. Trends Biochem Sci. 1996 Feb;21(2):50–50. [PubMed] [Google Scholar]
  27. Laundon C. H., Griffith J. D. Curved helix segments can uniquely orient the topology of supertwisted DNA. Cell. 1988 Feb 26;52(4):545–549. doi: 10.1016/0092-8674(88)90467-9. [DOI] [PubMed] [Google Scholar]
  28. Lavigne M., Herbert M., Kolb A., Buc H. Upstream curved sequences influence the initiation of transcription at the Escherichia coli galactose operon. J Mol Biol. 1992 Mar 20;224(2):293–306. doi: 10.1016/0022-2836(92)90995-v. [DOI] [PubMed] [Google Scholar]
  29. Law S. M., Bellomy G. R., Schlax P. J., Record M. T., Jr In vivo thermodynamic analysis of repression with and without looping in lac constructs. Estimates of free and local lac repressor concentrations and of physical properties of a region of supercoiled plasmid DNA in vivo. J Mol Biol. 1993 Mar 5;230(1):161–173. doi: 10.1006/jmbi.1993.1133. [DOI] [PubMed] [Google Scholar]
  30. Lewis M., Chang G., Horton N. C., Kercher M. A., Pace H. C., Schumacher M. A., Brennan R. G., Lu P. Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science. 1996 Mar 1;271(5253):1247–1254. doi: 10.1126/science.271.5253.1247. [DOI] [PubMed] [Google Scholar]
  31. Martino J. A., Olson W. K. Modeling protein-induced configurational changes in DNA minicircles. Biopolymers. 1997 Apr 5;41(4):419–430. doi: 10.1002/(SICI)1097-0282(19970405)41:4<419::AID-BIP6>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
  32. Moitoso de Vargas L., Kim S., Landy A. DNA looping generated by DNA bending protein IHF and the two domains of lambda integrase. Science. 1989 Jun 23;244(4911):1457–1461. doi: 10.1126/science.2544029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mossing M. C., Record M. T., Jr Upstream operators enhance repression of the lac promoter. Science. 1986 Aug 22;233(4766):889–892. doi: 10.1126/science.3090685. [DOI] [PubMed] [Google Scholar]
  34. Olson W. K., Marky N. L., Jernigan R. L., Zhurkin V. B. Influence of fluctuations on DNA curvature. A comparison of flexible and static wedge models of intrinsically bent DNA. J Mol Biol. 1993 Jul 20;232(2):530–554. doi: 10.1006/jmbi.1993.1409. [DOI] [PubMed] [Google Scholar]
  35. Olson W. K. Simulating DNA at low resolution. Curr Opin Struct Biol. 1996 Apr;6(2):242–256. doi: 10.1016/s0959-440x(96)80082-0. [DOI] [PubMed] [Google Scholar]
  36. Rippe K., Guthold M., von Hippel P. H., Bustamante C. Transcriptional activation via DNA-looping: visualization of intermediates in the activation pathway of E. coli RNA polymerase x sigma 54 holoenzyme by scanning force microscopy. J Mol Biol. 1997 Jul 11;270(2):125–138. doi: 10.1006/jmbi.1997.1079. [DOI] [PubMed] [Google Scholar]
  37. Rippe K., von Hippel P. H., Langowski J. Action at a distance: DNA-looping and initiation of transcription. Trends Biochem Sci. 1995 Dec;20(12):500–506. doi: 10.1016/s0968-0004(00)89117-3. [DOI] [PubMed] [Google Scholar]
  38. Rybenkov V. V., Vologodskii A. V., Cozzarelli N. R. The effect of ionic conditions on DNA helical repeat, effective diameter and free energy of supercoiling. Nucleic Acids Res. 1997 Apr 1;25(7):1412–1418. doi: 10.1093/nar/25.7.1412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Rybenkov V. V., Vologodskii A. V., Cozzarelli N. R. The effect of ionic conditions on the conformations of supercoiled DNA. I. Sedimentation analysis. J Mol Biol. 1997 Mar 28;267(2):299–311. doi: 10.1006/jmbi.1996.0876. [DOI] [PubMed] [Google Scholar]
  40. Santero E., Hoover T. R., North A. K., Berger D. K., Porter S. C., Kustu S. Role of integration host factor in stimulating transcription from the sigma 54-dependent nifH promoter. J Mol Biol. 1992 Oct 5;227(3):602–620. doi: 10.1016/0022-2836(92)90211-2. [DOI] [PubMed] [Google Scholar]
  41. Schleif R. DNA looping. Annu Rev Biochem. 1992;61:199–223. doi: 10.1146/annurev.bi.61.070192.001215. [DOI] [PubMed] [Google Scholar]
  42. Schlick T., Olson W. K. Supercoiled DNA energetics and dynamics by computer simulation. J Mol Biol. 1992 Feb 20;223(4):1089–1119. doi: 10.1016/0022-2836(92)90263-j. [DOI] [PubMed] [Google Scholar]
  43. Shore D., Baldwin R. L. Energetics of DNA twisting. I. Relation between twist and cyclization probability. J Mol Biol. 1983 Nov 15;170(4):957–981. doi: 10.1016/s0022-2836(83)80198-3. [DOI] [PubMed] [Google Scholar]
  44. Shore D., Langowski J., Baldwin R. L. DNA flexibility studied by covalent closure of short fragments into circles. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4833–4837. doi: 10.1073/pnas.78.8.4833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Stenger J. E., Tegtmeyer P., Mayr G. A., Reed M., Wang Y., Wang P., Hough P. V., Mastrangelo I. A. p53 oligomerization and DNA looping are linked with transcriptional activation. EMBO J. 1994 Dec 15;13(24):6011–6020. doi: 10.1002/j.1460-2075.1994.tb06947.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Su W., Middleton T., Sugden B., Echols H. DNA looping between the origin of replication of Epstein-Barr virus and its enhancer site: stabilization of an origin complex with Epstein-Barr nuclear antigen 1. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10870–10874. doi: 10.1073/pnas.88.23.10870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Su W., Porter S., Kustu S., Echols H. DNA-looping and enhancer activity: association between DNA-bound NtrC activator and RNA polymerase at the bacterial glnA promoter. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5504–5508. doi: 10.1073/pnas.87.14.5504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Vologodskii A. V., Levene S. D., Klenin K. V., Frank-Kamenetskii M., Cozzarelli N. R. Conformational and thermodynamic properties of supercoiled DNA. J Mol Biol. 1992 Oct 20;227(4):1224–1243. doi: 10.1016/0022-2836(92)90533-p. [DOI] [PubMed] [Google Scholar]
  49. Wedel A., Weiss D. S., Popham D., Dröge P., Kustu S. A bacterial enhancer functions to tether a transcriptional activator near a promoter. Science. 1990 Apr 27;248(4954):486–490. doi: 10.1126/science.1970441. [DOI] [PubMed] [Google Scholar]
  50. Yang Y., Westcott T. P., Pedersen S. C., Tobias I., Olson W. K. Effects of localized bending on DNA supercoiling. Trends Biochem Sci. 1995 Aug;20(8):313–319. doi: 10.1016/s0968-0004(00)89058-1. [DOI] [PubMed] [Google Scholar]
  51. Zhang P., Tobias I., Olson W. K. Computer simulation of protein-induced structural changes in closed circular DNA. J Mol Biol. 1994 Sep 23;242(3):271–290. doi: 10.1006/jmbi.1994.1578. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES