Differences Between Positively and Negatively Supercoiled DNA that Topoisomerases May Distinguish

  • Jonathan M. Fogg
  • Daniel J. CataneseJr
  • Graham L. Randall
  • Michelle C. Swick
  • Lynn Zechiedrich
Conference paper
Part of the The IMA Volumes in Mathematics and its Applications book series (IMA, volume 150)


In all living cells, DNA is homeostatically underwound relative to its lowest energy conformation, resulting in egative supercoiling. This underwinding of DNA is critical to the metabolism of DNA and, thus, is vital to cell survival. Enzymes called topoisomerases regulate and maintain the supercoiled state of DNA and are critical to the successful replication of the genome. These enzymes are major targets for drugs used in the treatment of bacterial infections and cancer. One puzzling phenomenon of the topoisomerase mechanism is how these enzymes, orders of magnitude smaller than their substrate, can search, recognize and act at a local level to affect global DNA topology. While the homeostatic state of DNA supercoiling in cells is negative, both positive and negative supercoils exist transiently. Because of the right-handed nature of the DNA helix, the positive and negative supercoils are not equivalent. Several computational and theoretical models have been developed in an effort to describe the features of both positively and negatively supercoiled DNA. These models have accurately predicted some of the phenomena observed in vivo. However, the over-simplifying assumptions cannot account for the different biological activities of positively and negatively supercoiled DNA. This review will discuss the models in place and the mathematical and energetic properties of this elegant molecule and the “machines that push it around.”


Torsional Rigidity Reverse Gyrase Negative Supercoiling Positive Supercoiling Intercalate Ethidium Bromide 
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.


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  1. Adrian M., ten Heggeler-Bordier B., Wahli W., Stasiak A.Z., Stasiak A., and Dubochet J. (1990). Direct visualization of supercoiled DNA molecules in solution. EMBO J. 9, 4551–4554.Google Scholar
  2. Allemand J.F., Bensimon D., Lavery R., and Croquette V. (1998). Stretched and overwound DNA forms a Pauling-like structure with exposed bases. Proc. Natl. Acad. Sci. USA 95, 14152–14157.Google Scholar
  3. Anderson P. and Bauer W. (1978) Supercoiling in closed circular DNA: dependence upon ion type and concentration. Biochemistry. 17, 594–601.Google Scholar
  4. Anderson V.E. and Osheroff N. (2001). Type II topoisomerases as targets for quinolone antibacterials: turning Dr. Jekyll into Mr. Hyde. Curr. Pharm. Des. 7, 337–353.Google Scholar
  5. Arai Y., Yasuda R., Akashi K., Harada Y., Miyata H., Kinosita K.J., and Itoh H. (1999). Tying a molecular knot with optical tweezers. Nature 399, 446–448.Google Scholar
  6. Arsuaga J., Vazquez M., Trigueros S., Sumners de W., and Roca J. (2002). Knotting probability of DNA molecules confined in restricted volumes: DNA knotting in phage capsids. Proc. Natl. Acad. Sci. USA 99, 5373–5377.Google Scholar
  7. Bacolla A. and Wells R.D. (2004). Non-B DNA conformations, genomic rearrange ments, and human disease. J. Biol. Chem. 279, 47411–47414.Google Scholar
  8. Baldwin G.S., Brooks N.J., Robson R.E., Wynveen A., Goldar A., Leikin S., Seddon J.M., and Kornyshev A.A. (2008) DNA double helices recognize mutual sequence homology in a protein free environment. J. Phys. Chem. B. 112, 1060–1064.Google Scholar
  9. Bates A.D. and Maxwell A. (2007). Energy coupling in type II topoisomerases: why do they hydrolyze ATP? Biochemistry 46, 7929–7941.Google Scholar
  10. Bednar J., Furrer P., Stasiak A., Dubochet J., Egelman E.H., and Bates A.D. (1994). The twist, writhe and overall shape of supercoiled DNA change during counterion-induced transition from a loosely to a tightly interwound superhelix. J. Mol. Biol. 235, 825–847.Google Scholar
  11. Belova G.I., Prasad R., Kozyavkin S.A., Lake J.A., Wilson S.H., and Slesarev A.I. (2001). A type IB topoisomerase with DNA repair activities. Proc. Natl. Acad. Sci. USA. 98, 6015–6020.Google Scholar
  12. Belova G.I., Prasad R., Nazimov I.V., Wilson S.H., and Slesarev A.I. (2002). The domain organization and properties of individual domains of DNA topoisomerase V, a type 1B topoisomerase with DNA repair activities. J. Biol. Chem. 277, 4959–4965.Google Scholar
  13. Benham C.J. (1979). Torsional stress and local denaturation in supercoiled DNA. Proc. Natl. Acad. Sci. USA 76, 3870–3874.Google Scholar
  14. Benham C.J. (1992). Energetics of the strand separation transition in superhelical DNA. J. Mol. Biol. 225, 835–847.Google Scholar
  15. Benham C.J. and Mielke S.P. (2005). DNA mechanics. Ann. Rev. Biomed. Eng. 7, 21–53.Google Scholar
  16. Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N., Weissig H., Shindyalov I.N., and Bourne P.E. (2000). The Protein Data Bank. Nucleic Acids Res. 28, 235–242.Google Scholar
  17. Boles T.C., White J.H., and Cozzarelli N.R. (1990). Structure of plectonemically supercoiled DNA. J. Mol. Biol. 213, 931–951.Google Scholar
  18. Bryant Z., Stone M.D., Gore J., Smith S.B., Cozzarelli N.R., and Bustamante C. (2003). Structural transitions and elasticity from torque measurements on DNA. Nature 424, 338–341.Google Scholar
  19. Buck G.R. and Zechiedrich E.L. (2004). DNA disentangling by type-2 topoisomerases. J. Mol. Biol. 340, 933–939.Google Scholar
  20. Burnier Y., Weber C., Flammini A., and Stasiak A. (2007). Local selection rules that can determine specific pathways of DNA unknotting by type II DNA topoisomerases. Nucleic Acids Res. 35, 5223–5231.Google Scholar
  21. Bustamante C., Bryant Z., and Smith S.B. (2003). Ten years of tension: single-molecule DNA mechanics. Nature 421, 423–427.Google Scholar
  22. Bustamante C., Marko J.F., Siggia E.D., and Smith S. (1994). Entropic elasticity of lambda-phage DNA. Science 265, 1599–1600.Google Scholar
  23. Calladine C.R. and Drew H.R. (1984) A base-centred explanation of the B-to-A transition in DNA. J. Mol. Biol. 178, 773–782.Google Scholar
  24. Camilloni G., Di Martino E., Caserta M., and di Mauro E. (1988). Eukaryotic DNA topoisomerase I reaction is topology dependent. Nucleic Acids Res. 14, 7071–7085.Google Scholar
  25. Camilloni G., Martino E., Di Mauro E., and Caserta M. (1989). Regulation of the function of eukaryotic DNA topoisomerase I: topological conditions for inactivity. Proc. Natl. Acad. Sci. USA 86, 3080–3084.Google Scholar
  26. Champoux J.J. (2001). DNA topoisomerases: structure, function, and mechanism. Annu. Rev. Biochem. 70, 369–413.Google Scholar
  27. Champoux J.J. (2002). Type IA DNA topoisomerases: strictly one step at a time. Proc. Natl. Acad. Sci. USA. 99, 11998–12000.Google Scholar
  28. Changela A., DiGate R.J., and Mondragon A. (2001). Crystal structure of a complex of a type IA DNA topoisomerase with a single-stranded DNA molecule. Nature 411, 1077–1081.Google Scholar
  29. Charvin G., Bensimon D., and Croquette V. (2003). Single-molecule study of DNA unlinking by eukaryotic and prokaryotic type-II topoisomerases. Proc. Natl. Acad. Sci. USA 100, 9820–9825.Google Scholar
  30. Charvin G., Strick T.R., Bensimon D., and Croquette V. (2005a). Topoisomerase IV bends and overtwists DNA upon binding. Biophys. J. 89, 384–392.Google Scholar
  31. Charvin G., Strick T.R., Bensimon D., and Croquette V. (2005b). Tracking topoisomerase activity at the single-molecule level. Ann. Rev. Biophys. Biomol. Struct. 34, 201–219.Google Scholar
  32. Cherny D.I. and Jovin T.M. (2001). Electron and scanning force microscopy studies of alterations in supercoiled DNA tertiary structure. J. Mol. Biol. 313, 295–307.Google Scholar
  33. Cloutier T.E. and Widom J. (2004). Spontaneous sharp bending of double-stranded DNA. Mol. Cell 14, 355–362.Google Scholar
  34. Cloutier T.E. and Widom J. (2005). DNA twisting flexibility and the formation of sharply looped protein-DNA complexes. Proc. Natl. Acad. Sci. USA 102, 3645–3650.Google Scholar
  35. Corbett K.D. and Berger J.M. (2004). Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases. Ann. Rev. Biophys. Biomol. Struct. 33, 95–118.Google Scholar
  36. Corbett K.D., Schoeffler A.J., Thomsen N.D., and Berger J.M. (2005). The structural basis for substrate specificity in DNA topoisomerase IV. J. Mol. Biol. 351, 545–561.Google Scholar
  37. Corbett K.D., Shultzaberger R.K., and Berger J.M. (2004). The C-terminal domain of DNA gyrase A adopts a DNA-bending beta-pinwheel fold. Proc. Natl. Acad. Sci. USA 101, 7293–7298.Google Scholar
  38. Cozzarelli N.R., Boles T.C., and White J.H. (1990). Primer on the topology and geometry of DNA supercoiling. In DNA topology and its biological effects. Cozzarelli N.R. and Wang, J.C. (eds.) Cold Spring Harbor Laboratory Press.Google Scholar
  39. Crick F.H. and Klug A. (1975). Kinky helix. Nature 255, 530–533.Google Scholar
  40. Crisona N.J. and Cozzarelli N.R. (2006). Alteration of Escherichia coli topoisomerase IV conformation upon enzyme binding to positively supercoiled DNA. J. Biol. Chem. 281, 18927–18932.Google Scholar
  41. Crisona N.J., Strick T.R., Bensimon D., Croquette V., and Cozzarelli N.R. (2000). Preferential relaxation of positively supercoiled DNA by E. coli topoisomerase IV in single-molecule and ensemble measurements. Genes Dev. 14, 2881–2892.Google Scholar
  42. Crooke E., Hwang D.S., Skarstad K., Thony B., and Kornberg A. (1991). E. coli minichromosome replication: regulation of initiation at oriC. Res. Microbiol. 142, 127–130.Google Scholar
  43. Crothers D.M., Drak J., Kahn J.D., and Levene S.D. (1992). DNA bending, flexibility, and helical repeat by cyclization kinetics. Methods Enzymol. 212, 3–29.Google Scholar
  44. Czapla L., Swigon D. and Olson W.K. (2006) Sequence-Dependent Effects in the Cyclization of Short DNA. J. Chem. Theory Comput. 2, 685–695.Google Scholar
  45. Deibler R.W., Mann J.K., Sumners D.W.L., and Zechiedrich L. (2007). Hinmediated DNA knotting and recombination promote replicon dysfunction and mutation. BMC Mol. Biol. 8, 44Google Scholar
  46. Dekker N.H., Rybenkov V.V., Duguet M., Crisona N.J., Cozzarelli N.R., Bensimon D., and Croquette V. (2002). The mechanism of type IA topoisomerases. Proc. Natl. Acad. Sci. USA 99, 12126–12131.Google Scholar
  47. Deutsch J.M. (1988). Theoretical studies of DNA during gel electrophoresis. Science 240, 922–924.Google Scholar
  48. Dickerson R.E. (1998). DNA bending: the prevalence of kinkiness and the virtues of normality. Nucleic Acids Res. 26, 1906–1926.Google Scholar
  49. Dong K.C. and Berger J.M. (2007). Structural basis for gate-DNA recognition and bending by type IIA topoisomerases. Nature 450, 1201–1205.Google Scholar
  50. Drake F.H., Hofmann G.A., Bartus H.F., Mattern M.R., Crooke S.T., and Mirabelli C.K. (1989). Biochemical and pharmacological properties of p170 and p180 forms of topoisomerase II. Biochemistry 28, 8154–8160.Google Scholar
  51. Du Q., Kotlyar A., and Vologodskii A. (2008). Kinking the double helix by bending deformation. Nucleic Acids Res. 36, 1120–1128.Google Scholar
  52. Du Q., Smith C., Shiffeldrim N., Vologodskaia M., and Vologodskii A. (2005). Cyclization of short DNA fragments and bending fluctuations of the double helix. Proc. Natl. Acad. Sci. USA 102, 5397–5402.Google Scholar
  53. Dunaway M. and Dröge P. (1989). Transactivation of the Xenopus rRNA gene promoter by its enhancer. Nature 341, 657–659.Google Scholar
  54. Drlica K., Malik M., Kerns R.J., Zhao X. (2008) Quinolone-mediated bacterial death. Antimicrob. Agents Chemother. 52, 385–392.Google Scholar
  55. Embleton M.L., Vologodskii A.V., and Halford S.E. (2004). Dynamics of DNA loop capture by the SfiI restriction endonuclease on supercoiled and relaxed DNA. J. Mol. Biol. 339, 53–66.Google Scholar
  56. Fogg J.M., Kolmakova N., Rees I., Magonov S., Hansma H., Perona J.J., and Zechiedrich E.L. (2006). Exploring writhe in supercoiled minicircle DNA. J. Phys: Condens. Matter 18, S145–S159.Google Scholar
  57. Forterre P. (2006) DNA topoisomerase V: a new fold of mysterious origin. Trends Biotechnol. 24, 245–247.Google Scholar
  58. Forterre P., Gribaldo S., Gadelle D., and Serre M.C. (2007) Origin and evolution of DNA topoisomerases. Biochimie. 89, 427–446.Google Scholar
  59. Fujimoto B.S. and Schurr J.M. (1990). Dependence of the torsional rigidity of DNA on base composition. Nature 344, 175–178.Google Scholar
  60. Fuller F.B. (1971). The writhing number of a space curve. Proc. Natl. Acad. Sci. USA 68, 815–819.MATHMathSciNetGoogle Scholar
  61. Fuller F.B. (1978). Decomposition of the linking of a closed ribbon: A problem of molecular biology. Proc. Natl. Acad. Sci. USA 75, 3557–3561.MATHMathSciNetGoogle Scholar
  62. Gellert M., Mizuuchi K., O’Dea M.H., and Nash H.A. (1976). DNA gyrase: An enzyme that introduces superhelical turns into DNA. Proc. Natl. Acad. Sci. USA 73, 3872–3876.Google Scholar
  63. Gore J., Bryant Z., Nollmann M., Le M.U., Cozzarelli N.R., and Bustamante C. (2006). DNA overwinds when stretched. Nature 442, 836–839.Google Scholar
  64. Gorin A.A, Zhurkin V.B., and Olson W.K. (1995) B-DNA twisting correlates with base-pair morphology. J. Mol. Biol. 247, 34–48.Google Scholar
  65. Gowers D.M. and Halford S.E. (2003). Protein motion from non-specific to specific DNA by three-dimensional routes aided by supercoiling. EMBO J. 22, 1410–1418.Google Scholar
  66. Grue P., Grasser A., Sehested M., Jensen P.B., Uhse A., Straub T., Ness W., and Boege F. (1998). Essential mitotic functions of DNA topoisomerase IIalpha are not adopted by topoisomerase IIbeta in human H69 cells. J. Biol. Chem. 273, 33660–33666.Google Scholar
  67. Hagerman P.J. (1988). Flexibility of DNA. Ann. Rev. Biophys. Biophys. Chem. 17, 265–286.Google Scholar
  68. Harris S.A., Laughton C.A., and Liverpool T.B. (2008). Mapping the phase diagram of the writhe of DNA nanocircles using atomistic molecular dynamics simulations. Nucleic Acids Res. 36, 21–29.Google Scholar
  69. Harris S.A., Sands Z.A., and Laughton C.A. (2005). Molecular dynamics simulations of duplex stretching reveal the importance of entropy in determining the biomechanical properties of DNA. Biophys. J. 88, 1684–1691.Google Scholar
  70. Heath P.J., Clendenning J.B., Fujimoto B.S., and Schurr J.M. (1996). Effect of bending strain on the torsion elastic constant of DNA. J. Mol. Biol. 260, 718–730.Google Scholar
  71. Heck M.M. and Earnshaw W.C. (1986). Topoisomerase II: A specific marker for cell proliferation. J. Cell. Biol. 103, 2569–2581.Google Scholar
  72. Hiasa H. and Marians K.J. (1996). Two distinct modes of topological processing during theta-type DNA replication. J. Biol. Chem. 271, 21529–21535.Google Scholar
  73. Hiasa H., Yousef D.O., and Marians K.J. (1996). DNA strand cleavage is required for replication fork arrest by a frozen topoisomerase-quinolone-DNA ternary complex. J. Biol. Chem. 271, 26424–26429.Google Scholar
  74. Hiller D.A., Rodriguez A.M., Perona J.J. Non-cognate enzyme-DNA complex: structural and kinetic analysis of EcoRV endonuclease bound to the EcoRI recognition site GAATTC. J. Mol. Biol. 354, 121–136.Google Scholar
  75. Higgins N.P. and Cozzarelli N.R. (1982). The binding of gyrase to DNA: analysis by retention by nitrocellulose filters. Nucleic Acids Res. 10, 6833–6847.Google Scholar
  76. Hopfield J.J. (1974). Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc. Natl. Acad. Sci. USA 71, 4135–4139.Google Scholar
  77. Horowitz D.S. and Wang J.C. (1984). Torsional rigidity of DNA and length dependence of the free energy of DNA supercoiling. J. Mol. Biol. 173, 75–91.Google Scholar
  78. Keller W. and Wendel I. (1975). Stepwise relaxation of supercoiled SV40 DNA. Cold Spring Harbor Symposia on Quantitative Biology 39 (Part 1), 199–208.Google Scholar
  79. Kikuchi A. and Asai K. (1984). Reverse gyrase–a topoisomerase which introduces positive superhelical turns into DNA. Nature 309, 677–681.Google Scholar
  80. Kim J.L., Nikolov D.B., and Burley S.K. (1993a). Co-crystal structure of TBP recognizing the minor groove of a TATA element. Nature 365, 520–527.Google Scholar
  81. Kim Y., Geiger J.H., Hahn S., and Sigler P.B. (1993b). Crystal structure of a yeast TBP/TATA-box complex. Nature 365, 512–520.Google Scholar
  82. Kirkegaard K. and Wang J.C. (1985). Bacterial DNA topoisomerase I can relax positively supercoiled DNA containing a single-stranded loop. J. Mol. Biol. 185, 625–637.Google Scholar
  83. Klenin K. and Langowski J. (2000). Computation of writhe in modeling of supercoiled DNA. Biopolymers 54, 307–317.Google Scholar
  84. Klenin K., Langowski J., and Vologodskii A.V. (2002). Computational analysis of the chiral action of type II DNA topoisomerases. J. Mol. Biol. 320, 359–367.Google Scholar
  85. Kondapi A.K., Mulpuri N., Mandraju R.K., Sasikaran B., and Subba Rao K. (2004) Analysis of age dependent changes of Topoisomerase II alpha and beta in rat brain. Int. J. Dev. Neurosci. 22, 19–30.Google Scholar
  86. Koster D.A., Croquette V., Dekker C., Shuman S., and Dekker N.H. (2005). Friction and torque govern the relaxation of DNA supercoils by eukaryotic topoisomerase IB. Nature 434, 671–674.Google Scholar
  87. Koster D.A., Palle K., Bot E.S., Bjornsti M.A., Dekker N.H. (2007). Antitumour drugs impede DNA uncoiling by topoisomerase I. Nature. 448, 213–217.Google Scholar
  88. Kramer P.R. and Sinden, R.R. (1997). Measurement of unrestrained negative supercoiling and topological domain size in living human cells. Biochemistry 36, 3151–3158.Google Scholar
  89. Kreuzer K.N. and Alberts B.M. (1984). Site-specific recognition of bacteriophage T4 DNA by T4 type II DNA topoisomerase and Escherichia coli DNA gyrase. J. Biol. Chem. 259, 5339–5346.Google Scholar
  90. Kreuzer K.N. and Cozzarelli N.R. (1979). Escherichia coli mutants thermosensitive for deoxyribonucleic acid gyrase subunit A: effects on deoxyribonucleic acid replication, transcription, and bacteriophage growth. J. Bacteriol. 140, 424–435.Google Scholar
  91. Krogh S., Mortensen U.H., Westergaard O., and Bonven B.J. (1991). Eukaryotic topoisomerase I-DNA interaction is stabilized by helix curvature. Nucleic Acids Res. 19, 1235–1241.Google Scholar
  92. LaMarr W.A., Sandman K.M., Reeve J.N., and Dedon P.C. (1997). Large scale preparation of positively supercoiled DNA using the archaeal histone HMf. Nucleic Acids Res. 25, 1660–1661.Google Scholar
  93. Lankas F., Lavery R., and Maddocks J.H. (2006). Kinking occurs during molecular dynamics simulations of small DNA minicircles. Structure 14, 1527–1534.Google Scholar
  94. Lee M.P., Sander M., and Hsieh T. (1989). Nuclease protection by Drosophila DNA topoisomerase II. Enzyme/DNA contacts at the strong topoisomerase II cleavage sites. J. Biol. Chem. 264, 21779–21787.Google Scholar
  95. Leppard J.B. and Champoux J.J. (2005). Human DNA topoisomerase I: relaxation, roles, and damage control. Chromosoma 114, 75–85.Google Scholar
  96. Levene S.D. and Crothers D.M. (1986). Topological distributions and the torsional rigidity of DNA. A Monte Carlo study of DNA circles. J. Mol. Biol. 189, 73–83.Google Scholar
  97. Levitt M. (1983) Protein folding by restrained energy minimization and molecular dynamics. J. Mol. Biol. 170, 723–764.Google Scholar
  98. Lewis M., Chang G., Horton N.C., Kercher M.A., Pace H.C., Schumacher M.A., Brennan R.G., and Lu P. (1996). Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science 271, 1247–1254.Google Scholar
  99. Lima C.D., Wang J.C., and Mondragon A. (1994). Three-dimensional structure of the 67 K N-terminal fragment of E. coli DNA topoisomerase I. Nature 367, 138–146.Google Scholar
  100. Lionnet T., Joubaud S., Lavery R., Bensimon D., and Croquette V. (2006). Wringing out DNA. Phys. Rev. Lett. 96, 178102.Google Scholar
  101. Liu C.C., Burke R.L., Hibner U., Barry J., and Alberts B. (1979a). Probing DNA replication mechanisms with the T4 bacteriophage in vitro system. Cold Spring Harbor Symposia on Quantitative Biology 43 (Part 1), 469–487.Google Scholar
  102. Liu D.J. and Day L.A. (1994). Pf1 virus structure: helical coat protein and DNA with paraxial phosphates. Science 265, 671–674.Google Scholar
  103. Liu L.F., Liu C.C., and Alberts B.M. (1979b). T4 DNA topoisomerase: a new ATP-dependent enzyme essential for initiation of T4 bacteriophage DNA replication. Nature 281, 456–461.Google Scholar
  104. Liu L.F. and Wang J.C. (1978). DNA-DNA gyrase complex: the wrapping of the DNA duplex outside the enzyme. Cell 15, 979–984.Google Scholar
  105. Liu L.F. and Wang J.C. (1987). Supercoiling of the DNA template during transcription. Proc. Natl. Acad. Sci. USA 84, 7024–7027.Google Scholar
  106. Liu Z., Mann J.K., Zechiedrich E.L., and Chan H.S. (2006a). Topological information embodied in local juxtaposition geometry provides a statistical mechanical basis for unknotting by type-2 DNA topoisomerases. J. Mol. Biol. 361, 268–285.Google Scholar
  107. Liu Z., Zechiedrich E.L., and Chan H.S. (2006b). Inferring global topology from local juxtaposition geometry: interlinking polymer rings and ramifications for topoisomerase action. Biophys. J. 90, 2344–2355.Google Scholar
  108. Liu Z., Deibler R.W., Chan H.S., and Zechiedrich (2008). Hooked on DNA: the why and how of DNA untangling. Nucleic Acids Res. in press.Google Scholar
  109. Liverpool T.B., Harris S.A., and Laughton C.A. (2008). Supercoiling and denaturation of DNA loops. Phys. Rev. Lett. 100, 238103.Google Scholar
  110. Lockshon D. and Morris D.R. (1983). Positively supercoiled plasmid DNA is produced by treatment of Escherichia coli with DNA gyrase inhibitors. Nucleic Acids Res. 11, 2999–3017.Google Scholar
  111. Luger K., Mader A.W., Richmond R.K., Sargent D.F., and Richmond T.J. (1997). Crystal structure of the nucleosome core particle at 2.8Å resolution. Nature 389, 251–260.Google Scholar
  112. Lyubchenko Y.L. (2004). DNA structure and dynamics: an atomic force microscopy study. Cell Biochem. Biophys. 41, 75–98.Google Scholar
  113. Madden K.R., Stewart L., and Champoux J.J. (1995). Preferential binding of human topoisomerase I to superhelical DNA. EMBO J. 14, 5399–5409.Google Scholar
  114. Maher L.J., 3rd (1998). Mechanisms of DNA bending. Current Opin. Chem. Biol. 2, 688–694.Google Scholar
  115. Maher L.J., 3rd (2006). DNA kinks available…if needed. Structure 14, 1479–1480.MathSciNetGoogle Scholar
  116. Manning G.S. (1969a). Limiting laws and counterion condensation in polyelectrolyte solutions. I. Colligative properties. J. Chem. Phys. 51, 924–933.Google Scholar
  117. Manning G.S. (1969b). Limiting laws and counterion condensation in polyelectrolyte solutions. II. Self-diffusion of the small ions. J. Chem. Phys. 51, 934–938.Google Scholar
  118. Marko J.F. and Siggia E.D. (1994). Bending and Twisting Elasticity of DNA. Macromolecules 27, 981–988.Google Scholar
  119. Martincic D. and Hande K.R. (2005). Topoisomerase II inhibitors. Cancer Chemother. Biol. Response Modif. 22, 101–121.Google Scholar
  120. Marvin D.A., Spencer M., Wilkins M.H., and Hamilton L.D. (1958) A new configuration of deoxyribonucleic acid. Nature 182, 387–388.Google Scholar
  121. McClellan J.A. and Lilley D.M. (1991). Structural alteration in alternating adenine-thymine sequences in positively supercoiled DNA. J. Mol. Biol. 219, 145–149.Google Scholar
  122. McClendon A.K., Dickey J.S., and Osheroff N. (2006a). The geometry of DNA supercoils modulates topoisomerase-mediated DNA cleavage and enzyme response to anticancer drugs. Biochemistry. 45, 3040–3050.Google Scholar
  123. McClendon A.K., Dickey J.S., and Osheroff N. (2006b). Ability of viral topoisomerase II to discern the handedness of supercoiled DNA: bimodal recognition of DNA geometry by type II enzymes. Biochemistry 45, 11674–11680.Google Scholar
  124. McClendon A.K. and Osheroff N. (2007). DNA topoisomerase II, genotoxicity, and cancer. Mut. Res. 623, 83–97.Google Scholar
  125. McClendon A.K., Rodriguez A.C., and Osheroff N. (2005). Human topoisomerase IIα rapidly relaxes positively supercoiled DNA: implications for enzyme action ahead of replication forks. J. Biol. Chem. 280, 39337–39345.Google Scholar
  126. Mizuuchi K., Gellert M., and Nash H.A. (1978). Involvement of supertwisted DNA in integrative recombination of bacteriophage lambda. J. Mol. Biol. 121, 375–392.Google Scholar
  127. Mondragon A. and DiGate R. (1999). The structure of Escherichia coli DNA topoisomerase III. Structure 7, 1373–1383.Google Scholar
  128. Muller M.T. (1985). Quantitation of eukaryotic topoisomerase I reactivity with DNA. Preferential cleavage of supercoiled DNA. Biochim. Biophys. Acta 824, 263–267.Google Scholar
  129. Musgrave D., Zhang X., and Dinger M. (2002). Archaeal genome organization and stress responses: implications for the origin and evolution of cellular life. Astrobiology 2, 241–253.Google Scholar
  130. Musgrave D.R., Sandman K.M., and Reeve J.N. (1991). DNA binding by the archaeal histone HMf results in positive supercoiling. Proc. Natl. Acad. Sci. USA 88, 10397–10401.Google Scholar
  131. Ninio J. (1975). Kinetic amplification of enzyme discrimination. Biochimie 57, 587–595.Google Scholar
  132. Nitiss J.L. (1998). Investigating the biological functions of DNA topoisomerases in eukaryotic cells. Biochim. Biophys. Acta. 1400, 63–81.Google Scholar
  133. Nöllmann M., Crisona N.J., and Arimondo P.B. (2007). Thirty years of Escherichia coli DNA gyrase: from in vivo function to single-molecule mechanism. Biochimie 89, 490–499.Google Scholar
  134. Nunes-Duby S.E., Smith-Mungo L.I., and Landy A. (1995). Single base-pair precision and structural rigidity in a small IHF-induced DNA loop. J. Mol. Biol. 253, 228–242.Google Scholar
  135. Olson W.K. (1996). Simulating DNA at low resolution. Current Opin. Struct. Biol. 6, 242–256.Google Scholar
  136. Olson W.K., Gorin A.A., Lu X.J., Hock L.M., and Zhurkin V.B. (1998). DNA sequence-dependent deformability deduced from protein-DNA crystal complexes. Proc. Natl. Acad. Sci. USA 95, 11163–11168.Google Scholar
  137. Osheroff N. (1986). Eukaryotic topoisomerase II. Characterization of enzyme turnover. J. Biol. Chem. 261, 9944–9950.Google Scholar
  138. Osheroff N. (1987). Role of the divalent cation in topoisomerase II mediated reactions. Biochemistry 26, 6402–6406.Google Scholar
  139. Osheroff N., Shelton E.R., and Brutlag D.L. (1983). DNA topoisomerase II from Drosophila melanogaster. Relaxation of supercoiled DNA. J. Biol. Chem 258, 9536–9543.Google Scholar
  140. Osheroff N. and Zechiedrich E.L. (1987). Calcium-promoted DNA cleavage by eukaryotic topoisomerase II: Trapping the covalent enzyme-DNA complex in an active form. Biochemistry 26, 4303–4309.Google Scholar
  141. Pack G.R., Wong L., and Lamm G. (1999). Divalent cations and the electrostatic potential around DNA: Monte Carlo and Poisson-Boltzmann calculations. Biopolymers 49, 575–590.Google Scholar
  142. Parvin J.D., McCormick R.J., Sharp P.A., and Fisher D.E. (1995). Pre-bending of a promoter sequence enhances affinity for the TATA-binding factor. Nature 373, 724–727.Google Scholar
  143. Pauling L. and Corey R.B. (1953). A proposed structure for the nucleic acids. Proc. Natl. Acad. Sci. USA 39, 84–97.Google Scholar
  144. Pavlicek J.W., Oussatcheva E.A., Sinden R.R., Potaman V.N., Sankey O.F., and Lyubchenko Y.L. (2004). Supercoiling-induced DNA bending. Biochemistry 43, 10664–10668.Google Scholar
  145. Peng H. and Marians K. (1995). The interaction of Escherichia coli topoisomerase IV with DNA. J. Biol. Chem. 270, 25286–25290.Google Scholar
  146. Pérez A., Lankas F., Luque F.J., Orozco M. (2008) Towards a molecular dynamics consensus view of B-DNA flexibility. Nucleic Acids Res. 36, 2379–2394.Google Scholar
  147. Perry K. and Mondragon A. (2003). Structure of a complex between E. coli DNA topoisomerase I and single-stranded DNA. Structure 11, 1349–1358.Google Scholar
  148. Pohl W.F. and Roberts G.W. (1978). Topological considerations in the theory of replication of DNA. J. Math. Biol. 6, 383–402.MathSciNetGoogle Scholar
  149. Pommier Y. (2006). Topoisomerase I inhibitors: camptothecins and beyond. Nat. Rev. Cancer 6, 789–802.Google Scholar
  150. Portugal J. and Rodriguez-Campos A. (1996). T7 RNA polymerase cannot transcribe through a highly knotted DNA template. Nucleic Acids Res. 24, 4890–4894.Google Scholar
  151. Randall G.L., Pettitt B.M., Buck G., and Zechiedrich E.L. (2006). Electrostatics of DNA-DNA juxtapositions: consequences for type II topoisomerase function. J. Phys: Condens. Matter 18, S173–S185.Google Scholar
  152. Redinbo M.R., Champoux J.J., and Hol W.G. (2000). Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA. Biochemistry 39, 6832–6840.Google Scholar
  153. Redinbo M.R., Stewart L., Champoux J.J., and Hol W.G. (1999). Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures. J. Mol. Biol. 292, 685–696.Google Scholar
  154. Redinbo M.R., Stewart L., Kuhn P., Champoux J.J., and Hol W.G. (1998). Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Science 279, 1504–1513.Google Scholar
  155. Reeve J.N., Sandman K., and Daniels C.J. (1997). Archaeal histones, nucleosomes, and transcription initiation. Cell 89, 999–1002.Google Scholar
  156. Rice P.A., Yang S., Mizuuchi K., and Nash H.A. (1996). Crystal structure of an IHF-DNA complex: a protein-induced DNA U-turn. Cell 87, 1295–1306.Google Scholar
  157. Richet E., Abcarian P., and Nash H.A. (1986). The interaction of recombination proteins with supercoiled DNA: defining the role of supercoiling in lambda integrative recombination. Cell 46, 1011–1021.Google Scholar
  158. Rodley G.A., Scobie R.S., Bates R.H.T., and Lewitt R.M. (1976) A possible conformation for double-stranded polynucleotides. Proc. Natl. Acad. Sci. USA. 73, 2929–2963.Google Scholar
  159. Rodriguez-Campos A. (1996). DNA knotting abolishes in vitro chromatin assembly. J. Biol. Chem. 271, 14150–14155.Google Scholar
  160. Rodriguez A.C. (2002). Studies of a positive supercoiling machine. Nucleotide hydrolysis and a multifunctional “latch” in the mechanism of reverse gyrase. J. Biol. Chem. 277, 29865–29873.Google Scholar
  161. Rybenkov V.V., Ullsperger C., Vologodskii A.V., and Cozzarelli N.R. (1997a). Simplification of DNA topology below equilibrium values by type II topoisomerases. Science 277, 690–693.Google Scholar
  162. Rybenkov V.V., Vologodskii A.V., and Cozzarelli N.R. (1997b). The effect of ionic conditions on DNA helical repeat, effective diameter, and free energy of supercoiling. Nucleic Acids Res. 25, 1412–1418.Google Scholar
  163. Saitta A.M., Soper P.D., Wasserman E., and Klein M.L. (1999). Influence of a knot on the strength of a polymer strand. Nature 399, 46–48.Google Scholar
  164. Schoeffler A.J. and Berger J.M. (2005). Recent advances in understanding structure-function relationships in the type II topoisomerase mechanism. Biochem. Soc. Trans. 33, 1465–1470.Google Scholar
  165. Schoeffler A.J. and Berger J.M. (2008). DNA topoisomerases: harnessing and constraining energy to govern chromosome topology. Quart. Rev. Biophys. 41, 41–101.Google Scholar
  166. Schvartzman J.B. and Stasiak A. (2004). A topological view of the replicon. EMBO Rep. 5, 256–261.Google Scholar
  167. Selvin P.R., Cook D.N., Pon N.G., Bauer W.R., Klein M.P., and Hearst J.E. (1992). Torsional rigidity of positively and negatively supercoiled DNA. Science 255, 82–85.Google Scholar
  168. Shore D. and Baldwin R.L. (1983a). Energetics of DNA twisting. I. Relation between twist and cyclization probability. J. Mol. Biol. 170, 957–981.Google Scholar
  169. Shore D. and Baldwin R.L. (1983b). Energetics of DNA twisting. II. Topoisomer analysis. J. Mol. Biol. 170, 983–1007.Google Scholar
  170. Shore D., Langowski J., and Baldwin R.L. (1981). DNA flexibility studied by covalent closure of short fragments into circles. Proc. Natl. Acad. Sci USA 78, 4833–4837.Google Scholar
  171. Sikorav J.L. and Jannink G. (1994). Kinetics of chromosome condensation in the presence of topoisomerases: a phantom chain model. Biophys. J. 66, 827–837.Google Scholar
  172. Smith S.B., Finzi L., and Bustamante C. (1992). Direct mechanical measurements of the elasticity of single DNA molecules by using magnetic beads. Science 258, 1122–1126.Google Scholar
  173. Snounou G. and Malcom A.D. (1983). Production of positively supercoiled DNA by netropsin. J. Mol. Biol. 167, 211–216.Google Scholar
  174. Sperrazza J.M., Register J.C. 3rd., and Griffith J. (1984). Electron microscopy can be used to measure DNA supertwisting. Gene 31, 17–22.Google Scholar
  175. Stewart L., Redinbo M.R., Qiu X., Hol W.G., and Champoux J.J. (1998). A model for the mechanism of human topoisomerase I. Science 279, 1534–1541.Google Scholar
  176. Stivers J.T., Harris T.K., and Mildvan A.S. (1997). Vaccinia DNA topoisomerase I: evidence supporting a free rotation mechanism for DNA supercoil relaxation. Biochemistry 36, 5212–5222.Google Scholar
  177. Stone M.D., Bryant Z., Crisona N.J., Smith S.B., Vologodskii A., Bustamante C., and Cozzarelli N.R. (2003). Chirality sensing by Escherichia coli topoisomerase IV and the mechanism of type II topoisomerases. Proc. Natl. Acad. Sci. USA 100, 8654–8659.Google Scholar
  178. Strick T.R., Allemand J.F., Bensimon D., Bensimon A., and Croquette V. (1996). The elasticity of a single supercoiled DNA molecule. Science 271, 1835–1837.Google Scholar
  179. Strick T.R., Allemand J.F., Bensimon D., and Croquette V. (1998). Behavior of supercoiled DNA. Biophys. J. 74, 2016–2028.Google Scholar
  180. Strick T.R., Allemand J.F., Bensimon D., and Croquette V. (2000a). Stress-induced structural transitions in DNA and proteins. Ann. Rev. Biophys. Biomol. Struct. 29, 523–543.Google Scholar
  181. Strick T.R., Bensimon D., and Croquette V. (1999). Micro-mechanical measurement of the torsional modulus of DNA. Genetica 106, 57–62.Google Scholar
  182. Strick T.R., Croquette V., and Bensimon D. (2000b). Single-molecule analysis of DNA uncoiling by a type II topoisomerase. Nature 404, 901–904.Google Scholar
  183. Svozil D., Sponer J.E., Marchan I., Pérez A., Cheatham T.E. 3rd, Forti. F., Luque F.J., Orozco M., Sponer J. (2008) Geometrical and electronic structure variability of the sugar-phosphate backbone in nucleic acids. J. Phys. Chem. B 112, 8188–8197.Google Scholar
  184. Taneja B., Patel A., Slesarev A., Mondragón A. (2006) Structure of the N-terminal fragment of topoisomerase V reveals a new family of topoisomerases. EMBO J. 25, 398–408.Google Scholar
  185. Taneja B., Schnurr B., Slesarev A., Marko J.F., Mondragón A. (2007) Topoisomerase V relaxes supercoiled DNA by a constrained swiveling mechanism. Proc. Natl. Acad. Sci. USA. 104, 14670–14675.Google Scholar
  186. Terry B.J., Jack W.E., and Modrich P. (1985). Facilitated diffusion during catalysis by EcoRI endonuclease. Nonspecific interactions in EcoRI catalysis. J. Biol. Chem. 260, 13130–13137.Google Scholar
  187. Thomsen B., Bendixen C., Lund K., Andersen A.H., Sorensen B.S., and Westergaard O. (1990). Characterization of the interaction between topoisomerase II and DNA by transcriptional footprinting. J. Mol. Biol. 215, 237–244.Google Scholar
  188. Timsit Y., Duplantier B., Jannink G., and Sikoravq J.-L. (1998). Symmetry and chirality in topoisomerases II-DNA crossover recognition. J. Mol. Biol. 284, 1289–1299.Google Scholar
  189. Timsit Y. and Moras D. (1994). DNA self-fitting: the double helix directs the geometry of its supramolecular assembly. EMBO J. 13, 2737–2746.Google Scholar
  190. Timsit Y., Shatzky-Schwartz M., and Shakked Z. (1999). Left-handed DNA crossovers. Implications for DNA-DNA recognition and structural alterations. J. Biomol. Struct. Dyn. 16, 775–785.Google Scholar
  191. Tolstorukov M.Y., Colasanti A.V., McCandlish D.M., Olson W.K., Zhurkin V.B. (2007) A novel roll-and-slide mechanism of DNA folding in chromatin: implications for nucleosome positioning. J. Mol. Biol. 371, 725–738.Google Scholar
  192. Travers A. and Muskhelishvili G. (2005). DNA supercoiling - a global transcriptional regulator for enterobacterial growth? Nat. Rev. Microbiol. 3, 157–169.Google Scholar
  193. Trigueros S., Salceda J., Bermudez I., Fernandez X., and Roca J. (2004). Asymmetric removal of supercoils suggests how topoisomerase II simplifies DNA topology. J. Mol. Biol. 335, 723–731.Google Scholar
  194. Ullsperger C. and Cozzarelli N.R. (1996). Contrasting enzymatic activities of topoisomerase IV and DNA gyrase from Escherichia coli. J. Biol. Chem. 271, 31549–31555.Google Scholar
  195. Vinograd J. and Lebowitz J. (1966). Physical and topological properties of circular DNA. J. Gen. Physiol. 49, 103–125.Google Scholar
  196. Vinograd J., Lebowitz J., Radloff R., Watson R., and Laipis P. (1965). The twisted circular form of polyoma viral DNA. Proc. Natl. Acad. Sci. USA 53, 1104–1111.Google Scholar
  197. Vologodskii A.V. and Cozzarelli N.R. (1996). Effect of supercoiling on the juxtaposition and relative orientation of DNA sites. Biophys. J. 70, 2548–2556.Google Scholar
  198. Vologodskii A.V., Levene S.D., Klenin K.V., Frank-Kamenetskii M., and Cozzarelli N.R. (1992). Conformational and thermodynamic properties of supercoiled DNA. J. Mol. Biol. 227, 1224–1243.Google Scholar
  199. Vologodskii A.V., Lukashin A.V., Anshelevich V.V., and Frank-Kamenetskii M.D. (1979). Fluctuations in superhelical DNA. Nucleic Acids Res. 6, 967–982.Google Scholar
  200. Vologodskii A.V., Zhang W., Rybenkov V.V., Podtelezhnikov A.A., Subramanian D., Griffith J.D., and Cozzarelli N.R. (2001). Mechanism of topology simplification by type II DNA topoisomerases. Proc. Natl. Acad. Sci. USA 98, 3045–3049.Google Scholar
  201. von Hippel P.H. (2007). From “simple” DNA-protein interactions to the macromolecular machines of gene expression. Ann. Rev. Biophys. Biomol. Struct. 36, 79–105.Google Scholar
  202. Wahle E. and Kornberg A. (1988). The partition locus of plasmid pSC101 is a specific binding site for DNA gyrase. EMBO J. 7, 1889–1895.Google Scholar
  203. Wang G. and Vasquez K.M. (2006). Non-B DNA structure-induced genetic instability. Mut. Res. 598, 103–119.Google Scholar
  204. Wang G. and Vasquez K.M. (2007). Z-DNA, an active element in the genome. Front. Biosci. 12, 4424–38.Google Scholar
  205. Wang J.C. (1971). Interaction between DNA and an Escherichia coli protein ω. J. Mol. Biol. 55, 523–533.Google Scholar
  206. Wang J.C. (1996). DNA topoisomerases. Annu. Rev. Biochem. 65, 635–692.Google Scholar
  207. Wang J.C. (2002). Cellular roles of DNA topoisomerases: A molecular perspective. Nat. Rev. Mol. Cell Biol. 3, 430–440.Google Scholar
  208. Watson J.D. and Crick F.H.C. (1953). Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid. Nature 171, 737–738.Google Scholar
  209. Weber C., Stasiak A., De Los Rios P., and Dietler G. (2006). Numerical simulation of gel electrophoresis of DNA knots in weak and strong electric fields. Biophys. J. 90, 3100–3105.Google Scholar
  210. Wells R.D. (2007). Non-B DNA conformations, mutagenesis and disease. Trends Biochem. Sci. 32, 271–278.Google Scholar
  211. Wells R.D., Dere R., Hebert M.L., Napierala M., and Son L.S. (2005). Advances in mechanisms of genetic instability related to hereditary neurological diseases. Nucleic Acids Res. 33, 3785–3798.Google Scholar
  212. White J.H. (1969). Self-linking and the Gauss integral in higher dimensions. Am. J. Math. 91, 693–728.MATHGoogle Scholar
  213. Whitson P.A., Hsieh W.T., Wells R.D., and Matthews K.S. (1987). Supercoiling facilitates lac operator-repressor-pseudooperator interactions. J. Biol. Chem. 262, 4943–4946.Google Scholar
  214. Wolters Kluwer Health, Pharmaceutical Audit Suite (PHAST), January to December 2006.Google Scholar
  215. Xu Y.C. and Bremer H. (1997). Winding of the DNA helix by divalent metal ions. Nucleic Acids Res. 25, 4067–4071.Google Scholar
  216. Yan J., Magnasco M.O., and Marko J.F. (1999). A kinetic proofreading mechanism for disentanglement of DNA by topoisomerases. Nature 401, 932–935.Google Scholar
  217. Yan J., Magnasco M.O., and Marko J.F. (2001). Kinetic proofreading can explain the supression of supercoiling of circular DNA molecules by type-II topoisomerases. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 63, 031909.Google Scholar
  218. Yin H., Wang M.D., Svoboda K., Landick R., Block S.M., and Gelles J. (1995). Transcription against an applied force. Science 270, 1653–1657.Google Scholar
  219. Zechiedrich E.L. and Cozzarelli N.R. (1995). Roles of topoisomerase IV and DNA gyrase in DNA unlinking during replication in Escherichia coli. Genes Dev. 9, 2859–2869.Google Scholar
  220. Zechiedrich E.L., Khodursky A.B., Bachellier S., Schneider R., Chen D., Lilley D.M., and Cozzarelli N.R. (2000). Roles of topoisomerases in maintaining steady-state DNA supercoiling in Escherichia coli. J. Biol. Chem. 275, 8103–8113.Google Scholar
  221. Zechiedrich E.L., Khodursky A.B., and Cozzarelli N.R. (1997). Topoisomerase IV, not gyrase, decatenates products of site-specific recombination in Escherichia coli. Genes Dev. 11, 2580–2592.Google Scholar
  222. Zechiedrich E.L. and Osheroff N. (1990). Eukaryotic topoisomerases recognize nucleic acid topology by preferentially interacting with DNA crossovers. EMBO J. 9, 4555–4562.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jonathan M. Fogg
    • 1
  • Daniel J. CataneseJr
    • 1
  • Graham L. Randall
    • 2
  • Michelle C. Swick
    • 2
    • 3
  • Lynn Zechiedrich
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of Molecular Virology and MicrobiologyBaylor College of MedicineHoustonUSA
  2. 2.Institutional Program in Structural and Computational Biology and Molecular Bio-physicsBaylor College of MedicineHoustonUSA
  3. 3.Interdepartmental Program in Cell and Molecular BiologyBaylor College of MedicineHoustonUSA
  4. 4.LZ: Funded by NIH Grant RO1 A1054830HoustonUSA

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