Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1986 Oct;5(10):2737–2744. doi: 10.1002/j.1460-2075.1986.tb04558.x

A computer aided thermodynamic approach for predicting the formation of Z-DNA in naturally occurring sequences.

P S Ho, M J Ellison, G J Quigley, A Rich
PMCID: PMC1167176  PMID: 3780676

Abstract

The ease with which a particular DNA segment adopts the left-handed Z-conformation depends largely on the sequence and on the degree of negative supercoiling to which it is subjected. We describe a computer program (Z-hunt) that is designed to search long sequences of naturally occurring DNA and retrieve those nucleotide combinations of up to 24 bp in length which show a strong propensity for Z-DNA formation. Incorporated into Z-hunt is a statistical mechanical model based on empirically determined energetic parameters for the B to Z transition accumulated to date. The Z-forming potential of a sequence is assessed by ranking its behavior as a function of negative superhelicity relative to the behavior of similar sized randomly generated nucleotide sequences assembled from over 80,000 combinations. The program makes it possible to compare directly the Z-forming potential of sequences with different base compositions and different sequence lengths. Using Z-hunt, we have analyzed the DNA sequences of the bacteriophage phi X174, plasmid pBR322, the animal virus SV40 and the replicative form of the eukaryotic adenovirus-2. The results are compared with those previously obtained by others from experiments designed to locate Z-DNA forming regions in these sequences using probes which show specificity for the left-handed DNA conformation.

Full text

PDF
2737

Selected References

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

  1. Barton J. K., Raphael A. L. Site-specific cleavage of left-handed DNA in pBR322 by lambda-tris(diphenylphenanthroline)cobalt(III). Proc Natl Acad Sci U S A. 1985 Oct;82(19):6460–6464. doi: 10.1073/pnas.82.19.6460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Depew D. E., Wang J. C. Conformational fluctuations of DNA helix. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4275–4279. doi: 10.1073/pnas.72.11.4275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Di Capua E., Stasiak A., Koller T., Brahms S., Thomae R., Pohl F. M. Torsional stress induces left-handed helical stretches in DNA of natural base sequence: circular dichroism and antibody binding. EMBO J. 1983;2(9):1531–1535. doi: 10.1002/j.1460-2075.1983.tb01619.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Drew H. R., Dickerson R. E. Structure of a B-DNA dodecamer. III. Geometry of hydration. J Mol Biol. 1981 Sep 25;151(3):535–556. doi: 10.1016/0022-2836(81)90009-7. [DOI] [PubMed] [Google Scholar]
  5. Ellison M. J., Feigon J., Kelleher R. J., 3rd, Wang A. H., Habener J. F., Rich A. An assessment of the Z-DNA forming potential of alternating dA-dT stretches in supercoiled plasmids. Biochemistry. 1986 Jun 17;25(12):3648–3655. doi: 10.1021/bi00360a026. [DOI] [PubMed] [Google Scholar]
  6. Ellison M. J., Kelleher R. J., 3rd, Wang A. H., Habener J. F., Rich A. Sequence-dependent energetics of the B-Z transition in supercoiled DNA containing nonalternating purine-pyrimidine sequences. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8320–8324. doi: 10.1073/pnas.82.24.8320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Feigon J., Wang A. H., van der Marel G. A., van Boom J. H., Rich A. Z-DNA forms without an alternating purine-pyrimidine sequence in solution. Science. 1985 Oct 4;230(4721):82–84. doi: 10.1126/science.4035359. [DOI] [PubMed] [Google Scholar]
  8. Greaves D. R., Patient R. K., Lilley D. M. Facile cruciform formation by an (A-T)34 sequence from a Xenopus globin gene. J Mol Biol. 1985 Oct 5;185(3):461–478. doi: 10.1016/0022-2836(85)90064-6. [DOI] [PubMed] [Google Scholar]
  9. Hagen F. K., Zarling D. A., Jovin T. M. Electron microscopy of SV40 DNA cross-linked by anti-Z DNA IgG. EMBO J. 1985 Mar;4(3):837–844. doi: 10.1002/j.1460-2075.1985.tb03706.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Haniford D. B., Pulleyblank D. E. Facile transition of poly[d(TG) x d(CA)] into a left-handed helix in physiological conditions. Nature. 1983 Apr 14;302(5909):632–634. doi: 10.1038/302632a0. [DOI] [PubMed] [Google Scholar]
  11. Haniford D. B., Pulleyblank D. E. Transition of a cloned d(AT)n-d(AT)n tract to a cruciform in vivo. Nucleic Acids Res. 1985 Jun 25;13(12):4343–4363. doi: 10.1093/nar/13.12.4343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Haschemeyer A. E., Rich A. Nucleoside conformations: an analysis of steric barriers to rotation about the glycosidic bond. J Mol Biol. 1967 Jul 28;27(2):369–384. doi: 10.1016/0022-2836(67)90026-5. [DOI] [PubMed] [Google Scholar]
  13. Herr W. Diethyl pyrocarbonate: a chemical probe for secondary structure in negatively supercoiled DNA. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8009–8013. doi: 10.1073/pnas.82.23.8009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Johnston B. H., Rich A. Chemical probes of DNA conformation: detection of Z-DNA at nucleotide resolution. Cell. 1985 Oct;42(3):713–724. doi: 10.1016/0092-8674(85)90268-5. [DOI] [PubMed] [Google Scholar]
  15. Jovin T. M., McIntosh L. P., Arndt-Jovin D. J., Zarling D. A., Robert-Nicoud M., van de Sande J. H., Jorgenson K. F., Eckstein F. Left-handed DNA: from synthetic polymers to chromosomes. J Biomol Struct Dyn. 1983 Oct;1(1):21–57. doi: 10.1080/07391102.1983.10507425. [DOI] [PubMed] [Google Scholar]
  16. Kmiec E. B., Angelides K. J., Holloman W. K. Left-handed DNA and the synaptic pairing reaction promoted by Ustilago rec1 protein. Cell. 1985 Jan;40(1):139–145. doi: 10.1016/0092-8674(85)90317-4. [DOI] [PubMed] [Google Scholar]
  17. Kmiec E. B., Holloman W. K. Homologous pairing of DNA molecules by Ustilago rec1 protein is promoted by sequences of Z-DNA. Cell. 1986 Feb 28;44(4):545–554. doi: 10.1016/0092-8674(86)90264-3. [DOI] [PubMed] [Google Scholar]
  18. Konopka A. K., Reiter J., Jung M., Zarling D. A., Jovin T. M. Concordance of experimentally mapped or predicted Z-DNA sites with positions of selected alternating purine-pyrimidine tracts. Nucleic Acids Res. 1985 Mar 11;13(5):1683–1701. doi: 10.1093/nar/13.5.1683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lafer E. M., Sousa R., Rich A. Anti-Z-DNA antibody binding can stabilize Z-DNA in relaxed and linear plasmids under physiological conditions. EMBO J. 1985 Dec 30;4(13B):3655–3660. doi: 10.1002/j.1460-2075.1985.tb04131.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miller F. D., Jorgenson K. F., Winkfein R. J., van de Sande J. H., Zarling D. A., Stockton J., Rattner J. B. Natural occurrence of left-handed (Z) regions in PM2 DNA. J Biomol Struct Dyn. 1983 Dec;1(3):611–620. doi: 10.1080/07391102.1983.10507468. [DOI] [PubMed] [Google Scholar]
  21. Nordheim A., Lafer E. M., Peck L. J., Wang J. C., Stollar B. D., Rich A. Negatively supercoiled plasmids contain left-handed Z-DNA segments as detected by specific antibody binding. Cell. 1982 Dec;31(2 Pt 1):309–318. doi: 10.1016/0092-8674(82)90124-6. [DOI] [PubMed] [Google Scholar]
  22. Nordheim A., Rich A. Negatively supercoiled simian virus 40 DNA contains Z-DNA segments within transcriptional enhancer sequences. Nature. 1983 Jun 23;303(5919):674–679. doi: 10.1038/303674a0. [DOI] [PubMed] [Google Scholar]
  23. Panyutin I., Lyamichev V., Mirkin S. A structural transition in d(AT)n.d(AT)n inserts within superhelical DNA. J Biomol Struct Dyn. 1985 Jun;2(6):1221–1234. doi: 10.1080/07391102.1985.10507634. [DOI] [PubMed] [Google Scholar]
  24. Peck L. J., Wang J. C. Energetics of B-to-Z transition in DNA. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6206–6210. doi: 10.1073/pnas.80.20.6206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pohl F. M., Jovin T. M. Salt-induced co-operative conformational change of a synthetic DNA: equilibrium and kinetic studies with poly (dG-dC). J Mol Biol. 1972 Jun 28;67(3):375–396. doi: 10.1016/0022-2836(72)90457-3. [DOI] [PubMed] [Google Scholar]
  26. Pulleyblank D. E., Haniford D. B., Morgan A. R. A structural basis for S1 nuclease sensitivity of double-stranded DNA. Cell. 1985 Aug;42(1):271–280. doi: 10.1016/s0092-8674(85)80122-7. [DOI] [PubMed] [Google Scholar]
  27. Pulleyblank D. E., Shure M., Tang D., Vinograd J., Vosberg H. P. Action of nicking-closing enzyme on supercoiled and nonsupercoiled closed circular DNA: formation of a Boltzmann distribution of topological isomers. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4280–4284. doi: 10.1073/pnas.72.11.4280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Revet B., Zarling D. A., Jovin T. M., Delain E. Different Z DNA forming sequences are revealed in phi X174 RFI by high resolution darkfield immuno-electron microscopy. EMBO J. 1984 Dec 20;3(13):3353–3358. doi: 10.1002/j.1460-2075.1984.tb02303.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rich A., Nordheim A., Wang A. H. The chemistry and biology of left-handed Z-DNA. Annu Rev Biochem. 1984;53:791–846. doi: 10.1146/annurev.bi.53.070184.004043. [DOI] [PubMed] [Google Scholar]
  30. Singleton C. K., Klysik J., Stirdivant S. M., Wells R. D. Left-handed Z-DNA is induced by supercoiling in physiological ionic conditions. Nature. 1982 Sep 23;299(5881):312–316. doi: 10.1038/299312a0. [DOI] [PubMed] [Google Scholar]
  31. Stockton J. F., Miller F. D., Jorgenson K. F., Zarling D. A., Morgan A. R., Rattner J. B., van de Sande J. H. Left-handed Z-DNA regions are present in negatively supercoiled bacteriophage PM2 DNA. EMBO J. 1983;2(12):2123–2128. doi: 10.1002/j.1460-2075.1983.tb01712.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vologodskii A. V., Frank-Kamenetskii M. D. Left-handed Z form in superhelical DNA: a theoretical study. J Biomol Struct Dyn. 1984 Jun;1(6):1325–1333. doi: 10.1080/07391102.1984.10507523. [DOI] [PubMed] [Google Scholar]
  33. Wang A. H., Gessner R. V., van der Marel G. A., van Boom J. H., Rich A. Crystal structure of Z-DNA without an alternating purine-pyrimidine sequence. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3611–3615. doi: 10.1073/pnas.82.11.3611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wang A. H., Quigley G. J., Kolpak F. J., Crawford J. L., van Boom J. H., van der Marel G., Rich A. Molecular structure of a left-handed double helical DNA fragment at atomic resolution. Nature. 1979 Dec 13;282(5740):680–686. doi: 10.1038/282680a0. [DOI] [PubMed] [Google Scholar]
  35. Wang A. J., Quigley G. J., Kolpak F. J., van der Marel G., van Boom J. H., Rich A. Left-handed double helical DNA: variations in the backbone conformation. Science. 1981 Jan 9;211(4478):171–176. doi: 10.1126/science.7444458. [DOI] [PubMed] [Google Scholar]
  36. Zarling D. A., Arndt-Jovin D. J., Robert-Nicoud M., McIntosh L. P., Thomae R., Jovin T. M. Immunoglobulin recognition of synthetic and natural left-handed Z DNA conformations and sequences. J Mol Biol. 1984 Jul 5;176(3):369–415. doi: 10.1016/0022-2836(84)90495-9. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES