Z-DNA: Conformational Flexibility of the DNA Double Helix

  • A. Nordheim
Conference paper
Part of the 35. Colloquium der Gesellschaft für Biologische Chemie 12.–14. April 1984 in Mosbach/Baden book series (MOSBACH, volume 35)


During the last 5 years new insights into the molecular structure of the DNA double helix have been obtained. An enhanced awareness of the conformational flexibility of the double-helical molecule has resulted (Cantor 1981; Pohl 1983; Rich 1983). The spectrum of the structural DNA polymorphism ranges from subtle, but distinct variations (e.g., Drew and Travers 1984; Frederick et al. 1984) of the classical right-handed B-DNA (Watson and Crick 1953) to the radically different left-handed Z-DNA (Wang et al. 1979). Two methodological developments allowed the recent progress in our understanding of DNA structure: first, rapid chemical synthesis of DNA oligonucleotides with defined nucleotide sequence and, second, recombinant DNA technology. The first technique greatly facilitated DNA X-ray crystallography by ensuring the supply of sufficient quantities of pure DNA material. The second method, in vitro recombination and cloning of DNA sequences, allowed biochemical characterization of individual DNA seaments of natural origin.


Polytene Chromosome Conformational Flexibility Supercoiled Plasmid Superhelical Density Superhelical Turn 
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. Arndt-Jovin DJ, Robert-Nicoud M, Zarling DA, Greider C, Weimer E, Jovin TM (1983) Left-handed Z-DNA in bands of acid-fixed polytene chromosomes. Proc Natl Acad Sci USA 80:4344–4348PubMedCrossRefGoogle Scholar
  2. Arnott S, Chandrasekaran R, Birdsall DL, Leslie AGW, Ratliff RL (1980) Left-handed DNA helices. Nature (Lond) 283:743–745CrossRefGoogle Scholar
  3. Azorin F, Nordheim A, Rich A (1983) Formation of Z-DNA in negatively supercoiled plasmids is sensitive to small changes in salt concentration within the physiological range. EMBO J 2:649–655PubMedGoogle Scholar
  4. Barton JK, Basile LA, Danishefsky A, Alexandrescu A (1984) Chiral probes for the handedness of DNA helices: Enantiomers of tris (4,7-diphenyl phenanthroline) ruthenium (II). Proc Natl Acad Sci USA 81:1961–1965PubMedCrossRefGoogle Scholar
  5. Becker MM, Wang JC (1984) Use of light for footprinting DNA in vivo. Nature (Lond) 309:682–687CrossRefGoogle Scholar
  6. Behe W, Felsenfeld G (1981) Effects of methylation on a synthetic polynucleotide: The B-Z transition in poly(dG-m5dC)-poly(dG-m5dC). Proc Natl Acad Sci USA 78: 1619–1623PubMedCrossRefGoogle Scholar
  7. Brahms S, Vergue J, Brahms JG, Di Capua E, Bucher P, Koller T (1982) Natural DNA sequences can form left-handed helices in low salt solution under conditions of topological constraint. J Mol Biol 162:473–493PubMedCrossRefGoogle Scholar
  8. Cantor CR (1981) DNA choreography. Cell 25:293–295PubMedCrossRefGoogle Scholar
  9. Castleman H, Hanau LH, Erlanger BF (1983) Stabilization of (dG-dC)n·(dG-dC)n in the Z conformation by a crosslinking reaction. Nucleic Acids Res 11:8421–8429PubMedCrossRefGoogle Scholar
  10. Church G, Gilbert W (1984) Genomic sequencing. Proc Natl Acad Sci USA 81:1991–1995PubMedCrossRefGoogle Scholar
  11. Crick FHC (1976) Linking numbers and nucleosomes. Proc Natl Acad Sci USA 73:2639–2643PubMedCrossRefGoogle Scholar
  12. Drew HR, Travers AA (1984) DNA structural variations in the E. coli tyr T promoter. Cell 37:491–502PubMedCrossRefGoogle Scholar
  13. Drew HR, Takano T, Tanaka S, Itakura K, Dickerson RE (1980) High salt d(CpGpCpG), a left-handed Z-DNA double helix. Nature (Lond) 286:567–573CrossRefGoogle Scholar
  14. Frederick CA et al. (1984) Kinked DNA in crystalline complex with EcoRI endonuclease. Nature (Lond) 309:327–331CrossRefGoogle Scholar
  15. Hanau LH, Santella R, Grunberger D, Erlanger BF (1984) An immunochemical examination of acetylaminofluorene-modified poly(dG-dC)-poly(dG-dC) in the Z-conformation. J Biol Chem 259:173–178PubMedGoogle Scholar
  16. Haniford DB, Pulleyblank DE (1983) Facile transition of poly [d(TG)·d(CA)] into a left-handed helix in physiological conditions. Nature (Lond) 302:632–634CrossRefGoogle Scholar
  17. Hill RJ, Stollar BD (1983) Dependence of Z-DNA antibody binding to polytene chromosomes on acid fixation and DNA torsional strain. Nature (Lond) 305:338–340CrossRefGoogle Scholar
  18. Jovin TM, McIntosh LP, Arndt-Jovin DJ, Zarling DA, Robert-Nicoud M, van de Sande JH, Jorgenson KF (1983) Left-handed DNA from synthetic polymers to chromosomes. J Biomol Struct Dynam 1:21–57Google Scholar
  19. Klevan L, Schumaker VN (1982) Stabilization of Z-DNA by poly-arginine near physiological ionic strength. Nucl Acids Res 10:6809–6817PubMedCrossRefGoogle Scholar
  20. Kilpatrick MW, Wei CF, Gray HR, Wells RD (1983) Bal 31 nuclease as a probe in concentrated salt for the B-Z DNA junction. Nucl Acids Res 11:3811–3822PubMedCrossRefGoogle Scholar
  21. Klysik J, Stirdivant SM, Larson JE, Hart PA, Wells RD (1981) Left-handed DNA in restriction fragments and a recombinant plasmid. Nature (Lond) 290:672–677CrossRefGoogle Scholar
  22. Kmiec EB, Holloman WK (1984) Synapsis promoted by Ustillago Rec I protein. Cell 36: 593–598PubMedCrossRefGoogle Scholar
  23. Lafer EM, Möller A, Nordheim A, Stollar BD, Rich A (1981) Antibodies specific for left-handed Z-DNA. Proc Natl Acad Sci USA 78:3546–3550PubMedCrossRefGoogle Scholar
  24. Lafer EM, Möller A, Valle RPC, Nordheim A, Rich A, Stollard BD (1983) Antibody recognition of Z-DNA. Cold Spring Harbor Symp Quant Biol 47:155–162PubMedGoogle Scholar
  25. Lang MC, Malfoy B, Freund AM, Daune M, Leng M (1982) Visualization of Z sequences in form V of pBR322 by immuno-electron microscopy. EMBO J 1:1149–1153PubMedGoogle Scholar
  26. Lemeunier F, Derbin C, Malfoy B, Leng M, Taillandier E (1982) Identification of left-handed Z-DNA by indirect immunofluorescence in polytene chromosomes of Chironomus thummi. Exp Cell Res 141:508PubMedCrossRefGoogle Scholar
  27. Lipps HJ, Nordheim A, Lafer EM, Ammermann D, Stollar BD, Rich A (1983) Antibodies against Z DNA react with the macronucleus but not the micronucleus of the hypotrichous ciliate Stylonychia mytilus. Cell 32:435–441PubMedCrossRefGoogle Scholar
  28. Luchnik AN, Bakayev W, Zbarsky IB, Georgiev GP (1982) Elastic torsional strain in DNA within a fraction of SV40 minichromosomes: relation to transcriptionally active chromatin. EMBO J 1:1353–1358PubMedGoogle Scholar
  29. Malfoy B, Hartmann B, Leng M (1981) The B to Z transition of poly(dG-dC)·poly(dG-dC) modified by some Platinum derivatives. Nucleic Acids Res 9:5659–5669PubMedCrossRefGoogle Scholar
  30. Malfoy B, Leng M (1981) Antiserum to Z-DNA. FEBS Lett 132:45–48PubMedCrossRefGoogle Scholar
  31. Malfoy B, Rousseau N, Leng M (1982) Interaction between antibodies to Z-form deoxyribonucleic acid and double-stranded polynucleotides. Biochemistry 21:4563–5467CrossRefGoogle Scholar
  32. McIntosh LP, Grieger I, Eckstein F, Zarling DA, van de Sande JH, Jovin TM (1983) Left-handed helical conformation of poly [d(A-m5C) ·d(G-T)]. Nature (Lond) 304: 83–86CrossRefGoogle Scholar
  33. Menzel R, Gellert M (1983) Regulation of the genes for E. coli DNA gyrase: homeostatic control of DNA supereoiling. Cell 34:105–113PubMedCrossRefGoogle Scholar
  34. Miller FD, Rattner JB, van de Sande JH (1983) Nucleosome-core assembly on B and Z forms of poly[d(G-m5c)]. Cold Spring Harbor Symp Quant Biol 47:571–575PubMedGoogle Scholar
  35. Möller A, Nordheim A, Nichols SR, Rich A (1981) 7-methylguanine residue in poly(dG-dC) · poly(dG-dC) facilitates Z-DNA formation. Proc Natl Acad Sci USA 78:4777–4781PubMedCrossRefGoogle Scholar
  36. Möller A, Gabriels JE, Lafer EM, Nordheim A, Rich A, Stollar BD (1982) Monoclonal antibodies recognize different parts of Z-DNA. J Biol Chem 257:12081–12085PubMedGoogle Scholar
  37. Möller A, Nordheim A, Kozlowski S, Patel DJ, Rich A (1984) Bromination stabilizes poly(dG-dC) in the Z-DNA form under low-salt conditions. Biochemistry 23:54–62PubMedCrossRefGoogle Scholar
  38. Morgenegg G, Celio MR, Malfoy B, Leng M, Kuenzle CC (1983) Z-DNA immunoreactivity in rat tissues. Nature (Lond) 303:540–543CrossRefGoogle Scholar
  39. Nickol J, Behe M, Felsenfeld G (1982) Effect of the B-Z transition in poly(dG-m5dC) · poly(dG-m5dC) on nucleosome formation. Proc Natl Acad Sci USA 79:1771–1775PubMedCrossRefGoogle Scholar
  40. Nordheim A, Rich A (1983a) The sequence (dC-dA)n·(dG-dT)n forms left-handed Z-DNA in negatively supercoiled plasmids. Proc Natl Acad Sci USA 80:1821–1825PubMedCrossRefGoogle Scholar
  41. Nordheim A, Rich A (1983b) Negatively supercoiled simian virus 40 DNA contains Z-DNA segments within transcriptional enhancer sequences. Nature (Lond) 303:674–679CrossRefGoogle Scholar
  42. Nordheim A, Pardue ML, Lafer EM, Möller A, Stollar BD, Rich A (1981) Antibodies to left-handed Z-DNA bind to interband regions of Drosophila polytene chromosomes. Nature (Lond) 294:417–422CrossRefGoogle Scholar
  43. Nordheim A, Lafer EM, Peck LJ, Wang JC, Stollar BD, Rich A (1982a) Negatively supercoiled plasmids contain left-handed Z-DNA segments as detected by specific antibody binding. Cell 31:309–318PubMedCrossRefGoogle Scholar
  44. Nordheim A, Tesser P, Azorin F, Kwon YH, Möller A, Rich A (1982b) Isolation of Drosophila proteins that bind selectively to left-handed Z-DNA. Proc Natl Acad Sci USA 79:7729–7733PubMedCrossRefGoogle Scholar
  45. Nordheim A, Hao WM, Wogan GN, Rich A (1983) Salt-induced conversion of B-DNA to Z-DNA inhibited by aflatoxin B1. Science (Wash DC) 219:1434–1436CrossRefGoogle Scholar
  46. Pardue ML, Nordheim A, Lafer EM, Stollar BD, Rich A (1983) Z-DNA and the polytene chromosome. Cold Spring Harbor Symp Quant Biol 47:171–176PubMedGoogle Scholar
  47. Patel DJ, Channel LL, Pohl FM (1979) “Alternating B-DNA” conformation for the oligo (dG-dC) duplex in high-salt solution. Proc Natl Acad Sci USA 76:2508–2511PubMedCrossRefGoogle Scholar
  48. Patel DJ, Kozlowski SA, Nordheim A, Rich A (1982) Right-handed and left-handed DNA: Studies of B- and Z-DNA by using proton nuclear Overhauser effect and pNMR. Proc Natl Acad Sci USA 79:1413–1417PubMedCrossRefGoogle Scholar
  49. Peck LJ, Wang JC (1983) Energetics of B-to-Z transition in DNA. Proc Natl Acad Sci USA 80:6206–6210PubMedCrossRefGoogle Scholar
  50. Peck LJ, Nordheim A, Rich A, Wang JC (1982) Flipping of cloned d(pCpG)n·d(pCpG)n DNA sequences from right- to left-handed helical structure by salt, co(III), or negative supercoiling. Proc Natl Acad Sci USA 79:4560–4564PubMedCrossRefGoogle Scholar
  51. Pohl FM (1976) Polymorphism of a synthetic DNA in solution. Nature (Lond) 260:365–366CrossRefGoogle Scholar
  52. Pohl FM (1983) Allosteric DNA. In: Sund, Vecger (eds) Mobility and recognition in cell biology. De Gruyter, New YorkGoogle Scholar
  53. Pohl FM, Jovin TM (1972) Salt-induced co-operative conformational change of a synthetic DNA: Equilibrium and kinetic studies with poly(dG-dC). J Mol Biol 67:375–396PubMedCrossRefGoogle Scholar
  54. Pohl FM, Ranade A, Stockburger M (1983) Laser Raman scattering of two double-helical forms of poly(dG-dC). Biochim Biophys Acta 335:85–92Google Scholar
  55. Pohl FM, Thomae R, DiCapua E (1982) Antibodies to Z-DNA interact with form V DNA. Nature (Lond) 300:545–546CrossRefGoogle Scholar
  56. Ramstein J, Leng M (1980) Salt-dependent dynamic structure of poly(dG-dC) ·poly(dG-dC). Nature (Lond) 288:413–414CrossRefGoogle Scholar
  57. Rich A (1983) Right-handed and left-handed DNA: conformational information in genetic material. Cold Spring Harbor Symp Quant Biol 47:1–12PubMedGoogle Scholar
  58. Rich A, Nordheim A, Wang AH-J (1984) The chemistry and biology of left-handed Z-DNA. Annu Rev Biochem 53:751CrossRefGoogle Scholar
  59. Robert-Nicoud M, Arndt-Jovin DJ, Zarling DA, Jovin TM (1984) Immunological detection of left-handed Z-DNA in isolated polytene chromosomes. Effects of ionic strength, pH, temperature and topological stress. EMBO J 3:721–731PubMedGoogle Scholar
  60. Rüssel WC, Precious B, Martin SR, Bayley PM (1983) Differential promotion and suppression of Z-B transitions in poly[d(G-C)] by histone subclasses, polyamino acids and polyamines. EMBO J 2:1647–1653Google Scholar
  61. Ryoji M, Worcel A (1984) Chromatin assembly in Xenopus oocytes: in vivo studies. Cell 37:21–32PubMedCrossRefGoogle Scholar
  62. Sage E, Leng M (1980) Conformation of poly(dG-dC) · poly(dG-dC) modified by the carcinogens N-acetoxy-N-acetyl-2-aminofluorene and N-hydroxy-N-2-aminofluorene. Proc Natl Acad Sci USA 77:4597–4601PubMedCrossRefGoogle Scholar
  63. Santella RM, Grunberger D, Weinstein IB, Rich A (1981) Induction of the Z conformation in poly (dG-dC) · poly(dG-dC) by binding of N-2-acetylaminofluorene to guanine residues. Proc Natl Acad Sci USA 78:1451–1455PubMedCrossRefGoogle Scholar
  64. Singleton CK, Klysik J, Stirdivant SM, Wells RD (1982) Left-handed Z-DNA is induced by supercoiling in physiological ionic conditions. Nature (Lond) 299:312–316CrossRefGoogle Scholar
  65. Singleton CK, Klysik J, Wells RD (1983) Conformational flexibility of junctions between contiguous B- and Z-DNAs in supercoiled plasmids. Proc Natl Acad Sci USA 80:2447PubMedCrossRefGoogle Scholar
  66. Stettler UH, Weber H, Koller T, Weissmann C (1979) Preparation and characterization of form V DNA, the doublex DNA resulting from association of complementary, circular single-stranded DNA. J Mol Biol 131:21–40PubMedCrossRefGoogle Scholar
  67. Sutherland JC, Griffin KP, Keck PC, Takacs PZ (1981) Z-DNA: vacuum ultraviolet circular dichroism. Proc Natl Acad Sci USA 78:4801–4804PubMedCrossRefGoogle Scholar
  68. Thamann TJ, Lord RC, Wang AH-J, Rich A (1981) The high-salt form of poly(dG-dC) · poly(dG-dC) is left-handed Z-DNA: Raman spectra of crystals and solutions. Nucleic Acids Res 9:5443–5457PubMedCrossRefGoogle Scholar
  69. Thomae R, Beck S, Pohl FM (1983) Isolation of Z-DNA-containing plasmids. Proc Natl Acad Sci USA 80:5500–5553CrossRefGoogle Scholar
  70. Thomas TJ, Bloomfield VA (1983) Chain flexibility and hydrodynamics of the B and Z forms of poly(dG-dC) · poly(dG-dC). Nucleic Acids Res 11:1919–1930PubMedCrossRefGoogle Scholar
  71. Ushay HM, Santella RM, Caradonna JP, Grunberger D, Lippard SJ (1982) Binding of [(dien)PtCl]cl to poly (dG-dC) · poly (dG-dC) facilitates the B → Z conformational transition. Nucleic Acids Res 10:3573–3588PubMedCrossRefGoogle Scholar
  72. van de Sande JH, Jovin TM (1982) Z* DNA, the left-handed helical form of poly[d(G-C)] in MgCl2-ethanol, is biologically active. EMBO J 1:115–120PubMedGoogle Scholar
  73. Viegas-Péquignot E, Derbin C, Malfoy B, Taillander E, Leng M, Dutrillaux B (1983) Z-DNA immunoreactivity in fixed metaphase chromosomes of primates. Proc Natl Acad Sci USA 80:5890–5894PubMedCrossRefGoogle Scholar
  74. Wang AH-J, Quigley GJ, Kolpak FJ, Crawford JL, van Boom JH, van der Marel G, Rich A (1979) Molecular structure of a left-handed double helical DNA fragment at atomic resolution. Nature (Lond) 282:680–686CrossRefGoogle Scholar
  75. Wang AH-J, Quigley GJ, Kolpak FJ, van der Marel G, van Boom JH, Rich A (1981) Left-handed double helical DNA: variations in the backbone conformation. Science (Wash DC) 211:171–176CrossRefGoogle Scholar
  76. Wang JC (1980) Superhelical DNA. Trends Biochem Sci 5:219–222CrossRefGoogle Scholar
  77. Watson DJ, Crick FH (1953) Molecular structure of nucleic acid: a structure for deoxyribose nucleic acid. Nature (Lond) 171:737–738CrossRefGoogle Scholar
  78. Wells RD, Miglietta JJ, Klysik J, Larson JE, Stirdivant SM, Zacharias W (1982) Spectroscopic studies on acetylaminofluorene-modified (dT-dG)n · (dC-dA)n suggest a left-handed conformation. J Biol Chem 257:10166–10171PubMedGoogle Scholar
  79. Wu H-M, Crothers DM (1984) The locus of sequence-directed and protein-induced DNA bending. Nature (Lond) 308:509–513CrossRefGoogle Scholar
  80. Zacharias W, Larson JE, Klysik J, Stirdivant SM, Wells RD (1982) Conditions which cause the right-handed to left-handed DNA conformational transitions. J Biol Chem 257:2775–2782PubMedGoogle Scholar
  81. Zarling DA, McIntosh LP, Arndt-Jovin DJ, Robert-Nicoud M, Jovin TM (1984) Interaction of Anti-poly [d(G-Br5C)] IgG with synthetic, viral and cellular Z-DNA. J Biomol Struct Dynam 1:1081–1107Google Scholar
  82. Zarling DA, Arndt-Jovin DJ, Robert-Nicoud M, McIntosh LP, Thomae R, Jovin TM (to be published 1984) Immunological recognition of synthetic and natural left-handed Z-DNA conformations and sequences. J Mol BiolGoogle Scholar
  83. Zimmermann SB (1982) The three-dimensional structure of DNA. Annu Rev Biochem 51:395–427CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1984

Authors and Affiliations

  • A. Nordheim
    • 1
  1. 1.Zentrum für Molekulare Biologie der Universität HeidelbergHeidelbergGermany

Personalised recommendations