, Volume 120, Issue 4, pp 323–334 | Cite as

The torsional state of DNA within the chromosome

  • Joaquim RocaEmail author


Virtually all processes of the genome biology affect or are affected by the torsional state of DNA. Torsional energy associated with an altered twist facilitates or hinders the melting of the double helix, its molecular interactions, and its spatial folding in the form of supercoils. Yet, understanding how the torsional state of DNA is modulated remains a challenging task due to the multiplicity of cellular factors involved in the generation, transmission, and dissipation of DNA twisting forces. Here, an overview of the implication of DNA topoisomerases, DNA revolving motors, and other DNA interactions that determine local levels of torsional stress in bacterial and eukaryotic chromosomes is provided. Particular emphasis is made on the experimental approaches being developed to assess the torsional state of intracellular DNA and its organization into topological domains.


Psoralen Torsional Stress Eukaryotic Chromosome Topological Domain Topological Boundary 
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.



This study was supported by Spanish grants BFU2008-00366, AGAUR 2009 SGR01222, and by Xarxa de Referencia en Biotecnologia de la Generalitat de Catalunya.


  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. Alexandrov AI, Cozzarelli NR, Holmes VF, Khodursky AB, Peter BJ, Postow L, Rybenkov V, Vologodskii AV (1999) Mechanisms of separation of the complementary strands of DNA during replication. Genetica 106:131–140PubMedCrossRefGoogle Scholar
  3. Anderson P, Bauer W (1978) Supercoiling in closed circular DNA: dependence upon ion type and concentration. Biochemistry 17:594–601PubMedCrossRefGoogle Scholar
  4. Bancaud A, Wagner G, Conde ESN, Lavelle C, Wong H, Mozziconacci J, Barbi M, Sivolob A, Le Cam E, Mouawad L, Viovy JL, Victor JM, Prunell A (2007) Nucleosome chiral transition under positive torsional stress in single chromatin fibers. Mol Cell 27:135–147PubMedCrossRefGoogle Scholar
  5. Baxter J, Diffley JF (2008) Topoisomerase II inactivation prevents the completion of DNA replication in budding yeast. Mol Cell 30:790–802PubMedCrossRefGoogle Scholar
  6. Bennink ML, Leuba SH, Leno GH, Zlatanova J, de Grooth BG, Greve J (2001) Unfolding individual nucleosomes by stretching single chromatin fibers with optical tweezers. Nat Struct Biol 8:606–610PubMedCrossRefGoogle Scholar
  7. Bermudez I, Garcia-Martinez J, Perez-Ortin JE, Roca J (2010) A method for genome-wide analysis of DNA helical tension by means of psoralen-DNA photobinding. Nucleic Acids Res 38:e182PubMedCrossRefGoogle Scholar
  8. Bliska JB, Cozzarelli NR (1987) Use of site-specific recombination as a probe of DNA structure and metabolism in vivo. J Mol Biol 194:205–218PubMedCrossRefGoogle Scholar
  9. Boeger H, Bushnell DA, Davis R, Griesenbeck J, Lorch Y, Strattan JS, Westover KD, Kornberg RD (2005) Structural basis of eukaryotic gene transcription. FEBS Lett 579:899–903PubMedCrossRefGoogle Scholar
  10. Boles TC, White JH, Cozzarelli NR (1990) Structure of plectonemically supercoiled DNA. J Mol Biol 213:931–951PubMedCrossRefGoogle Scholar
  11. Byrd K, Corces VG (2003) Visualization of chromatin domains created by the gypsy insulator of Drosophila. J Cell Biol 162:565–574PubMedCrossRefGoogle Scholar
  12. Cavalli G, Bachmann D, Thoma F (1996) Inactivation of topoisomerases affects transcription-dependent chromatin transitions in rDNA but not in a gene transcribed by RNA polymerase II. EMBO J 15:590–597PubMedGoogle Scholar
  13. Clark DJ, Felsenfeld G (1991) Formation of nucleosomes on positively supercoiled DNA. EMBO J 10:387–395PubMedGoogle Scholar
  14. Clark DJ, Ghirlando R, Felsenfeld G, Eisenberg H (1993) Effect of positive supercoiling on DNA compaction by nucleosome cores. J Mol Biol 234:297–301PubMedCrossRefGoogle Scholar
  15. Claudet C, Angelov D, Bouvet P, Dimitrov S, Bednar J (2005) Histone octamer instability under single molecule experiment conditions. J Biol Chem 280:19958–19965PubMedCrossRefGoogle Scholar
  16. Conti C, Sacca B, Herrick J, Lalou C, Pommier Y, Bensimon A (2007) Replication fork velocities at adjacent replication origins are coordinately modified during DNA replication in human cells. Mol Biol Cell 18:3059–3067PubMedCrossRefGoogle Scholar
  17. Cook PR (1999) The organization of replication and transcription. Science 284:1790–1795PubMedCrossRefGoogle Scholar
  18. Crisona NJ, Kanaar R, Gonzalez TN, Zechiedrich EL, Klippel A, Cozzarelli NR (1994) Processive recombination by wild-type gin and an enhancer-independent mutant. Insight into the mechanisms of recombination selectivity and strand exchange. J Mol Biol 243:437–457PubMedCrossRefGoogle Scholar
  19. Cui Y, Bustamante C (2000) Pulling a single chromatin fiber reveals the forces that maintain its higher-order structure. Proc Natl Acad Sci USA 97:127–132PubMedCrossRefGoogle Scholar
  20. Darzacq X, Shav-Tal Y, de Turris V, Brody Y, Shenoy SM, Phair RD, Singer RH (2007) In vivo dynamics of RNA polymerase II transcription. Nat Struct Mol Biol 14:796–806PubMedCrossRefGoogle Scholar
  21. Davie JR (1997) Nuclear matrix, dynamic histone acetylation and transcriptionally active chromatin. Mol Biol Rep 24:197–207PubMedCrossRefGoogle Scholar
  22. Delius H, Worcel A (1974) Letter: electron microscopic visualization of the folded chromosome of Escherichia coli. J Mol Biol 82:107–109PubMedCrossRefGoogle Scholar
  23. Deng S, Stein RA, Higgins NP (2005) Organization of supercoil domains and their reorganization by transcription. Mol Microbiol 57:1511–1521PubMedCrossRefGoogle Scholar
  24. Depew DE, Wang JC (1975) Conformational fluctuations of DNA helix. Proc Natl Acad Sci USA 72:4275–4279PubMedCrossRefGoogle Scholar
  25. DiNardo S, Voelkel KA, Sternglanz R, Reynolds AE, Wright A (1982) Escherichia coli DNA topoisomerase I mutants have compensatory mutations in DNA gyrase genes. Cell 31:43–51PubMedCrossRefGoogle Scholar
  26. Drlica K (1992) Control of bacterial DNA supercoiling. Mol Microbiol 6:425–433PubMedCrossRefGoogle Scholar
  27. Drlica K, Rouviere-Yaniv J (1987) Histonelike proteins of bacteria. Microbiol Rev 51:301–319PubMedGoogle Scholar
  28. Droge P (1994) Protein tracking-induced supercoiling of DNA: a tool to regulate DNA transactions in vivo? Bioessays 16:91–99PubMedCrossRefGoogle Scholar
  29. Drolet M (2006) Growth inhibition mediated by excess negative supercoiling: the interplay between transcription elongation, R-loop formation and DNA topology. Mol Microbiol 59:723–730PubMedCrossRefGoogle Scholar
  30. Dulbecco R, Vogt M (1963) Evidence for a ring structure of polyoma virus DNA. Proc Natl Acad Sci USA 50:236–243PubMedCrossRefGoogle Scholar
  31. French SL, Sikes ML, Hontz RD, Osheim YN, Lambert TE, El Hage A, Smith MM, Tollervey D, Smith JS, Beyer AL (2011) Distinguishing the roles of topoisomerases I and II in relief of transcription-induced torsional stress in yeast rRNA genes. Mol Cell Biol 31:482–494PubMedCrossRefGoogle Scholar
  32. Furlong JC, Sullivan KM, Murchie AI, Gough GW, Lilley DM (1989) Localized chemical hyperreactivity in supercoiled DNA: evidence for base unpairing in sequences that induce low-salt cruciform extrusion. Biochemistry 28:2009–2017PubMedCrossRefGoogle Scholar
  33. Gartenberg MR, Wang JC (1992) Positive supercoiling of DNA greatly diminishes mRNA synthesis in yeast. Proc Natl Acad Sci USA 89:11461–11465PubMedCrossRefGoogle Scholar
  34. Gartenberg MR, Wang JC (1993) Identification of barriers to rotation of DNA segments in yeast from the topology of DNA rings excised by an inducible site-specific recombinase. Proc Natl Acad Sci USA 90:10514–10518PubMedCrossRefGoogle Scholar
  35. Gray HB Jr, Upholt WB, Vinograd J (1971) A buoyant method for the determination of the superhelix density of closed circular DNA. J Mol Biol 62:1–19PubMedCrossRefGoogle Scholar
  36. Guo F, Adhya S (2007) Spiral structure of Escherichia coli HUalphabeta provides foundation for DNA supercoiling. Proc Natl Acad Sci USA 104:4309–4314PubMedCrossRefGoogle Scholar
  37. Happel N, Doenecke D (2009) Histone H1 and its isoforms: contribution to chromatin structure and function. Gene 431:1–12PubMedCrossRefGoogle Scholar
  38. Higgins NP, Yang X, Fu Q, Roth JR (1996) Surveying a supercoil domain by using the gamma delta resolution system in Salmonella typhimurium. J Bacteriol 178:2825–2835PubMedGoogle Scholar
  39. Huertas P, Aguilera A (2003) Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Mol Cell 12:711–721PubMedCrossRefGoogle Scholar
  40. Jackson DA, Dickinson P, Cook PR (1990) The size of chromatin loops in HeLa cells. EMBO J 9:567–571PubMedGoogle Scholar
  41. Joshi RS, Pina B, Roca J (2010) Positional dependence of transcriptional inhibition by DNA torsional stress in yeast chromosomes. Embo J 29:740–748PubMedCrossRefGoogle Scholar
  42. Jupe ER, Sinden RR, Cartwright IL (1995) Specialized chromatin structure domain boundary elements flanking a Drosophila heat shock gene locus are under torsional strain in vivo. Biochemistry 34:2628–2633PubMedCrossRefGoogle Scholar
  43. Kavenoff R, Bowen BC (1976) Electron microscopy of membrane-free folded chromosomes from Escherichia coli. Chromosoma 59:89–101PubMedCrossRefGoogle Scholar
  44. Kavenoff R, Ryder OA (1976) Electron microscopy of membrane-associated folded chromosomes of Escherichia coli. Chromosoma 55:13–25PubMedCrossRefGoogle Scholar
  45. Kawamura R, Pope LH, Christensen MO, Sun M, Terekhova K, Boege F, Mielke C, Andersen AH, Marko JF (2010) Mitotic chromosomes are constrained by topoisomerase II-sensitive DNA entanglements. J Cell Biol 188:653–663PubMedCrossRefGoogle Scholar
  46. Kim RA, Wang JC (1989) Function of DNA topoisomerases as replication swivels in Saccharomyces cerevisiae. J Mol Biol 208:257–267PubMedCrossRefGoogle Scholar
  47. Koster DA, Crut A, Shuman S, Bjornsti MA, Dekker NH (2010) Cellular strategies for regulating DNA supercoiling: a single-molecule perspective. Cell 142:519–530PubMedCrossRefGoogle Scholar
  48. Kouzine F, Levens D (2007) Supercoil-driven DNA structures regulate genetic transactions. Front Biosci 12:4409–4423PubMedCrossRefGoogle Scholar
  49. Kouzine F, Sanford S, Elisha-Feil Z, Levens D (2008) The functional response of upstream DNA to dynamic supercoiling in vivo. Nat Struct Mol Biol 15:146–154PubMedCrossRefGoogle Scholar
  50. Kramer PR, Sinden RR (1997) Measurement of unrestrained negative supercoiling and topological domain size in living human cells. Biochemistry 36:3151–3158PubMedCrossRefGoogle Scholar
  51. Lavelle C, Victor JM, Zlatanova J (2010) Chromatin fiber dynamics under tension and torsion. Int J Mol Sci 11:1557–1579PubMedCrossRefGoogle Scholar
  52. Lilley DM (1986) DNA supercoiling and DNA structure. Biochem Soc Trans 14:211–213PubMedGoogle Scholar
  53. Lim HM, Lewis DE, Lee HJ, Liu M, Adhya S (2003) Effect of varying the supercoiling of DNA on transcription and its regulation. Biochemistry 42:10718–10725PubMedCrossRefGoogle Scholar
  54. Liu J, Kouzine F, Nie Z, Chung HJ, Elisha-Feil Z, Weber A, Zhao K, Levens D (2006) The FUSE/FBP/FIR/TFIIH system is a molecular machine programming a pulse of c-myc expression. EMBO J 25:2119–2130PubMedCrossRefGoogle Scholar
  55. Ljungman M, Hanawalt PC (1995) Presence of negative torsional tension in the promoter region of the transcriptionally poised dihydrofolate reductase gene in vivo. Nucleic Acids Res 23:1782–1789PubMedCrossRefGoogle Scholar
  56. Maurer S, Fritz J, Muskhelishvili G, Travers A (2006) RNA polymerase and an activator form discrete subcomplexes in a transcription initiation complex. EMBO J 25:3784–3790PubMedCrossRefGoogle Scholar
  57. Menzel R, Gellert M (1983) Regulation of the genes for E. coli DNA gyrase: homeostatic control of DNA supercoiling. Cell 34:105–113PubMedCrossRefGoogle Scholar
  58. Mihardja S, Spakowitz AJ, Zhang Y, Bustamante C (2006) Effect of force on mononucleosomal dynamics. Proc Natl Acad Sci USA 103:15871–15876PubMedCrossRefGoogle Scholar
  59. Mondal N, Zhang Y, Jonsson Z, Dhar SK, Kannapiran M, Parvin JD (2003) Elongation by RNA polymerase II on chromatin templates requires topoisomerase activity. Nucleic Acids Res 31:5016–5024PubMedCrossRefGoogle Scholar
  60. Morham SG, Kluckman KD, Voulomanos N, Smithies O (1996) Targeted disruption of the mouse topoisomerase I gene by camptothecin selection. Mol Cell Biol 16:6804–6809PubMedGoogle Scholar
  61. Nelson P (1999) Transport of torsional stress in DNA. Proc Natl Acad Sci USA 96:14342–14347PubMedCrossRefGoogle Scholar
  62. Norton VG, Imai BS, Yau P, Bradbury EM (1989) Histone acetylation reduces nucleosome core particle linking number change. Cell 57:449–457PubMedCrossRefGoogle Scholar
  63. Palecek E (1991) Local supercoil-stabilized DNA structures. Crit Rev Biochem Mol Biol 26:151–226PubMedCrossRefGoogle Scholar
  64. Peter BJ, Arsuaga J, Breier AM, Khodursky AB, Brown PO, Cozzarelli NR (2004) Genomic transcriptional response to loss of chromosomal supercoiling in Escherichia coli. Genome Biol 5:R87PubMedCrossRefGoogle Scholar
  65. Postow L, Hardy CD, Arsuaga J, Cozzarelli NR (2004) Topological domain structure of the Escherichia coli chromosome. Genes Dev 18:1766–1779PubMedCrossRefGoogle Scholar
  66. Prunell A (1998) A topological approach to nucleosome structure and dynamics: the linking number paradox and other issues. Biophys J 74:2531–2544PubMedCrossRefGoogle Scholar
  67. Pruss GJ, Drlica K (1989) DNA supercoiling and prokaryotic transcription. Cell 56:521–523PubMedCrossRefGoogle Scholar
  68. Rahmouni AR, Wells RD (1989) Stabilization of Z DNA in vivo by localized supercoiling. Science 246:358–363PubMedCrossRefGoogle Scholar
  69. Rahmouni AR, Wells RD (1992) Direct evidence for the effect of transcription on local DNA supercoiling in vivo. J Mol Biol 223:131–144PubMedCrossRefGoogle Scholar
  70. Razin SV, Iarovaia OV, Sjakste N, Sjakste T, Bagdoniene L, Rynditch AV, Eivazova ER, Lipinski M, Vassetzky YS (2007) Chromatin domains and regulation of transcription. J Mol Biol 369:597–607PubMedCrossRefGoogle Scholar
  71. Rhodes D, Klug A (1980) Helical periodicity of DNA determined by enzyme digestion. Nature 286:573–578PubMedCrossRefGoogle Scholar
  72. Rimsky S (2004) Structure of the histone-like protein H-NS and its role in regulation and genome superstructure. Curr Opin Microbiol 7:109–114PubMedCrossRefGoogle Scholar
  73. Roca J (1995) The mechanisms of DNA topoisomerases. Trends Biochem Sci 20:156–160PubMedCrossRefGoogle Scholar
  74. Roca J (2009a) Topoisomerase II: a fitted mechanism for the chromatin landscape. Nucleic Acids Res 37:721–730PubMedCrossRefGoogle Scholar
  75. Roca J (2009b) Two-dimensional agarose gel electrophoresis of DNA topoisomers. Methods Mol Biol 582:27–37PubMedCrossRefGoogle Scholar
  76. Salceda J, Fernandez X, Roca J (2006) Topoisomerase II, not topoisomerase I, is the proficient relaxase of nucleosomal DNA. EMBO J 25:2575–2583PubMedCrossRefGoogle Scholar
  77. Schneider R, Lurz R, Luder G, Tolksdorf C, Travers A, Muskhelishvili G (2001) An architectural role of the Escherichia coli chromatin protein FIS in organising DNA. Nucleic Acids Res 29:5107–5114PubMedCrossRefGoogle Scholar
  78. Schoeffler AJ, Berger JM (2008) DNA topoisomerases: harnessing and constraining energy to govern chromosome topology. Q Rev Biophys 41:41–101PubMedCrossRefGoogle Scholar
  79. Schvartzman JB, Stasiak A (2004) A topological view of the replicon. EMBO Rep 5:256–261PubMedCrossRefGoogle Scholar
  80. Sekedat MD, Fenyo D, Rogers RS, Tackett AJ, Aitchison JD, Chait BT (2010) GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome. Mol Syst Biol 6:353PubMedCrossRefGoogle Scholar
  81. Shure M, Vinograd J (1976) The number of superhelical turns in native virion SV40 DNA and minicol DNA determined by the band counting method. Cell 8:215–226PubMedCrossRefGoogle Scholar
  82. Simpson RT, Thoma F, Brubaker JM (1985) Chromatin reconstituted from tandemly repeated cloned DNA fragments and core histones: a model system for study of higher order structure. Cell 42:799–808PubMedCrossRefGoogle Scholar
  83. Sinden RR, Pettijohn DE (1981) Chromosomes in living Escherichia coli cells are segregated into domains of supercoiling. Proc Natl Acad Sci USA 78:224–228PubMedCrossRefGoogle Scholar
  84. Sinden RR, Ussery DW (1992) Analysis of DNA structure in vivo using psoralen photobinding: measurement of supercoiling, topological domains, and DNA–protein interactions. Methods Enzymol 212:319–335PubMedCrossRefGoogle Scholar
  85. Sinden RR, Carlson JO, Pettijohn DE (1980) Torsional tension in the DNA double helix measured with trimethylpsoralen in living E. coli cells: analogous measurements in insect and human cells. Cell 21:773–783PubMedCrossRefGoogle Scholar
  86. Stros M (2010) HMGB proteins: interactions with DNA and chromatin. Biochim Biophys Acta 1799:101–113PubMedGoogle Scholar
  87. Travers A, Muskhelishvili G (2005a) DNA supercoiling—a global transcriptional regulator for enterobacterial growth? Nat Rev Microbiol 3:157–169PubMedCrossRefGoogle Scholar
  88. Travers A, Muskhelishvili G (2005b) Bacterial chromatin. Curr Opin Genet Dev 15:507–514PubMedCrossRefGoogle Scholar
  89. Uemura T, Yanagida M (1984) Isolation of type I and II DNA topoisomerase mutants from fission yeast: single and double mutants show different phenotypes in cell growth and chromatin organization. EMBO J 3:1737–1744PubMedGoogle Scholar
  90. Ullsperger C, Cozzarelli NR (1996) Contrasting enzymatic activities of topoisomerase IV and DNA gyrase from Escherichia coli. J Biol Chem 271:31549–31555PubMedCrossRefGoogle Scholar
  91. Vinograd J, Lebowitz J, Radloff R, Watson R, Laipis P (1965) The twisted circular form of polyoma viral DNA. Proc Natl Acad Sci USA 53:1104–1111PubMedCrossRefGoogle Scholar
  92. Vologodskii AV, Cozzarelli NR (1994) Conformational and thermodynamic properties of supercoiled DNA. Annu Rev Biophys Biomol Struct 23:609–643PubMedCrossRefGoogle Scholar
  93. Vologodskii A, Cozzarelli NR (1996) Effect of supercoiling on the juxtaposition and relative orientation of DNA sites. Biophys J 70:2548–2556PubMedCrossRefGoogle Scholar
  94. Wang JC (1971) Interaction between DNA and an Escherichia coli protein omega. J Mol Biol 55:523–533PubMedCrossRefGoogle Scholar
  95. Wang JC (1974) The degree of unwinding of the DNA helix by ethidium. I. Titration of twisted PM2 DNA molecules in alkaline cesium chloride density gradients. J Mol Biol 89:783–801PubMedCrossRefGoogle Scholar
  96. Wang JC (1985) DNA topoisomerases: nature’s solution to the topological ramifications of the double-helix structure of DNA. Harvey Lect 81:93–110PubMedGoogle Scholar
  97. Wang MD, Schnitzer MJ, Yin H, Landick R, Gelles J, Block SM (1998) Force and velocity measured for single molecules of RNA polymerase. Science 282:902–907PubMedCrossRefGoogle Scholar
  98. Weil R, Vinograd J (1963) The cyclic helix and cyclic coil forms of polyoma viral DNA. Proc Natl Acad Sci USA 50:730–738PubMedCrossRefGoogle Scholar
  99. White JH (1969) Self-linking and the Gauss integral in higher dimensions. Am J Math 91:693–728CrossRefGoogle Scholar
  100. Worcel A, Burgi E (1972) On the structure of the folded chromosome of Escherichia coli. J Mol Biol 71:127–147PubMedCrossRefGoogle Scholar
  101. Wuite GJ, Smith SB, Young M, Keller D, Bustamante C (2000) Single-molecule studies of the effect of template tension on T7 DNA polymerase activity. Nature 404:103–106PubMedCrossRefGoogle Scholar
  102. Yusufzai TM, Tagami H, Nakatani Y, Felsenfeld G (2004) CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol Cell 13:291–298PubMedCrossRefGoogle Scholar
  103. Zechiedrich EL, Khodursky AB, Bachellier S, Schneider R, Chen D, Lilley DM, Cozzarelli NR (2000) Roles of topoisomerases in maintaining steady-state DNA supercoiling in Escherichia coli. J Biol Chem 275:8103–8113PubMedCrossRefGoogle Scholar
  104. Zlatanova J, Seebart C, Tomschik M (2008) The linker-protein network: control of nucleosomal DNA accessibility. Trends Biochem Sci 33:247–253PubMedCrossRefGoogle Scholar

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© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Instituto de Biología Molecular de Barcelona, CSICBarcelonaSpain

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