Conformation and Energetics of Supercoiled DNA: Experimental and Theoretical Studies

  • S. D. Levene
Part of the Nucleic Acids and Molecular Biology book series (NUCLEIC, volume 8)


Although DNA supercoiling has been known for years to be intimately associated with many aspects of transcription, replication, and recombination, the structure of superhelical DNA in solution has only recently begun to be understood. Because significant supercoiling requires a DNA molecule at least 1kb in size, high-resolution techniques such as X-ray diffraction and NMR spectroscopy are not applicable. Much of the classical information about the structure of supercoiled DNA comes from hydro-dynamic and related techniques such as sedimentation, light-, X-ray-, and neutron-scattering. These techniques are sensitive to the large-scale polymer behavior of macromolecules reflected in quantities such as the mean chain radius, but give little insight into details of structure without a model for polymer-chain organization. Electron microscopy (EM) has been frequently used as a semiquantitative tool for examining the structure of supercoiled DNA; however, the images of superhelical molecules visualized by electron microscopy have only recently been quantitatively analyzed and reconciled with theoretical models (Boles et al. 1990). The interpretation of EM data requires assumptions about effects of heavy-metal staining, dehydration, shadowing, and the interaction of DNA with the grid surface, all of which are difficult to test. Gel electrophoresis is one potentially powerful technique that is highly sensitive to the topological state of a DNA molecule; however, the effect of supercoiling on electrophoretic mobility remains poorly understood.


Helical Twist Molecular Dynamic Technique Molecular Mechanic Model Bend Locus Trial Conformation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adrian M, ten Heggeler-Bordier B, Wahli W, Stasiak AZ, Stasiak A, Dubochet J (1990) Direct visualization of supercoiled DNA molecules in solution. EMBO J 9:4551–4554PubMedGoogle Scholar
  2. Bauer WR, Benham CJ (1993) The free energy, enthalpy and entropy of native and partially denatured closed circular DNA. J Mol Biol 234:1184–1196PubMedCrossRefGoogle Scholar
  3. Bauer WR, Lund RA, White JH (1993) Twist and writhe of a DNA loop containing intrinsic bends. Proc Natl Acad Sci USA 90:833–837PubMedCrossRefGoogle Scholar
  4. Bednar J, Furrer P, Stasiak A, Dubochet J, Egelman E, Bates AD (1994) 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 235:825–847PubMedCrossRefGoogle Scholar
  5. Boles TC, White JH, Cozzarelli NR (1990) Structure of plectonemically supercoiled DNA. J Mol Biol 213:931–951PubMedCrossRefGoogle Scholar
  6. Brady GW, Fein DB, Lambertson H, Grassian V, Foos D, Benham CJ (1983) X-ray scattering from the superhelix in circular DNA. Proc Natl Acad Sci USA 80:741–744PubMedCrossRefGoogle Scholar
  7. Camerini-Otero RD, Felsenfeld G (1978) A simple model of DNA superhelices in solution. Proc Natl Acad Sci USA 75:1708–1712PubMedCrossRefGoogle Scholar
  8. Cozzarelli NR, Boles TC, White JH (1990) Primer on the topology and geometry of DNA supercoiling. In: Cozzarelli NR, Wang JC (eds) DNA topology and its biological effects. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 139–184Google Scholar
  9. Dubochet J, Adrian M, Chang J-J, Homo J-C, Lepault J, McDowall AW, Schultz P (1988) Cryo-electron microscopy of vitrified specimens. Q Rev Biophys 21:129–228PubMedCrossRefGoogle Scholar
  10. Dubochet J, Adrian M, Dustin I, Furrer P, Stasiak A (1992) Cryoelectron microscopy of DNA molecules in solution. In: Lilley DMJ, Dahlberg JE (eds) DNA structures (part A: synthesis and physical analysis of DNA). Academic Press, San Diego, pp 507–518 (Methods in Enzymology, vol 211)CrossRefGoogle Scholar
  11. Dustin I, Furrer P, Stasiak A, Dubochet J, Langowski J, Egelman E (1991) Spatial visualization of DNA in solution. J Struct Biol 107:15–21PubMedCrossRefGoogle Scholar
  12. Frank-Kamenetskii MD, Vologodskii AV (1981) Topological aspects of the physics of polymers: the theory and its biological applications. Sov Phys-Usp 24:679–697CrossRefGoogle Scholar
  13. Gogol EP, Young MC, Kubasek WL, Jarvis TC, von Hippel PH (1992) Cryoelectron microscopic visualization of functional subassemblies of the bacteriophage T4 DNA replication complex. J Mol Biol 224:395–412PubMedCrossRefGoogle Scholar
  14. Hao M-H, Olson WK (1989a) Global equilibrium configurations of supercoiled DNA. Macromolecules 22:3292–3303CrossRefGoogle Scholar
  15. Hao M-H, Olson WK (1989b) Molecular modeling and energy refinement of supercoiled DNA. J Biomol Struct Dyn 7:661–692PubMedGoogle Scholar
  16. Harris RA, Hearst JE (1966) On polymer dynamics. J Chem Phys 44:2595–2602CrossRefGoogle Scholar
  17. Hearst JE, Hunt NG (1991) Statistical mechanical theory for the plectonemic DNA supercoil. J Chem Phys 95:9322–9328CrossRefGoogle Scholar
  18. Hunt NG, Hearst JE (1991) Elastic model of DNA supercoiling in the infinite-length limit. J Chem Phys 95:9329–9336CrossRefGoogle Scholar
  19. Klenin KV, Vologodskii AV, Anshelevich VV, Klisko VY, Dykhne AM, Frank-Kamenetskii MD (1989) Variance of writhe for wormlike DNA rings with excluded volume. J Biomol Struct Dyn 6:707–714PubMedGoogle Scholar
  20. Klenin KV, Vologodskii AV, Anshelevich VV, Dykhne AM, Frank-Kamenetskii MD (1991) Computer simulation of DNA supercoiling. J Mol Biol 217:413–419PubMedCrossRefGoogle Scholar
  21. Laundon CH, Griffith JD (1988) Curved helix segments can uniquely orient the topology of supertwisted DNA. Cell 52:545–549PubMedCrossRefGoogle Scholar
  22. LeBret M (1979) Catastrophic variation of twist and writhing of circular DNAs with constraint? Biopolymers 18:1709–1725CrossRefGoogle Scholar
  23. LeBret M (1984) Twist and writhing in short circular DNAs according to first-order elasticity. Biopolymers 23:1835–1867CrossRefGoogle Scholar
  24. Malhotra A, Gabb HA, Harvey SC (1993) Modeling large nucleic acids. Curr Opinion Struct Biol 3:241–246CrossRefGoogle Scholar
  25. McCammon JA, Harvey SC (1987) Dynamics of proteins and nucleic acids. Cambridge University Press, CambridgeGoogle Scholar
  26. Olson WK, Zhang P (1991) Computer simulation of DNA supercoiling. In: Langone JJ (ed) Molecular design and modeling; concepts and applications. Academic Press, San Diego, pp 403–432 (Methods in enzymology, vol 203)Google Scholar
  27. Post CB, Zimm BH (1982) Light-scattering study of DNA condensation: competition between collapse and aggregation. Biopolymers 21:2139–2160PubMedCrossRefGoogle Scholar
  28. Rhoades M, Thomas CA (1968) The P22 bacteriophage DNA molecule. II. Circular intracellular forms. J Mol Biol 37:41–61PubMedCrossRefGoogle Scholar
  29. Rybenkov VV, Cozzarelli NR, Vologodskii AV (1993) Probability of DNA knotting and the effective diameter of the DNA double helix. Proc Natl Acad Sci USA 90:5307–5311PubMedCrossRefGoogle Scholar
  30. Schlick T, Olson WK (1992a) Supercoiled DNA energetics and dynamics by computer simulation. J Mol Biol 223:1089–1119PubMedCrossRefGoogle Scholar
  31. Schlick T, Olson WK (1992b) Trefoil knotting revealed by molecular dynamics simulations of supercoiled DNA. Science 257:1110–1115PubMedCrossRefGoogle Scholar
  32. Seidl A, Hinz H-J (1984) The free energy of DNA supercoiling is enthalpy-determined. Proc Natl Acad Sci USA 81:1312–1316PubMedCrossRefGoogle Scholar
  33. Shaw SY, Wang JC (1993) Knotting of a DNA chain during ring closure. Science 260:533–536PubMedCrossRefGoogle Scholar
  34. Tan RK, Harvey SC (1989) Molecular mechanics model of supercoiled DNA. J Mol Biol 205:573–591PubMedCrossRefGoogle Scholar
  35. Vologodskii AV, Cozzarelli NR (1994) Conformational and thermodynamic properties of supercoiled DNA. Annu Rev Biophys Biomol Struct 23:609–643PubMedCrossRefGoogle Scholar
  36. Vologodskii AV, Levene SD, Klenin KV, Frank-Kamenetskii M, Cozzarelli NR (1992) Conformational and thermodynamic properties of supercoiled DNA. J Mol Biol 227:1224–1243PubMedCrossRefGoogle Scholar
  37. White JH (1969) Self-linking and the Gauss integral in higher dimensions. Am J Math 91:693–728CrossRefGoogle Scholar
  38. White JH (1989) An introduction to the geometry and topology of DNA structure. In: Waterman MS (ed) Mathematical methods for DNA sequences. CRC Press, Boca Raton, pp 225–253Google Scholar
  39. Yang Y, Tobias I, Olson WK (1992) Finite element analysis of DNA supercoiling. J Chem Phys 98:1673–1686CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • S. D. Levene
    • 1
  1. 1.Program in Molecular and Cell BiologyThe University of Texas at DallasRichardsonUSA

Personalised recommendations