• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. Oct 1986; 5(10): 2737–2744.
PMCID: PMC1167176

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

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

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Barton JK, Raphael AL. 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. [PMC free article] [PubMed]
  • Depew DE, Wang JC. Conformational fluctuations of DNA helix. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4275–4279. [PMC free article] [PubMed]
  • Di Capua E, Stasiak A, Koller T, Brahms S, Thomae R, Pohl FM. 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. [PMC free article] [PubMed]
  • Drew HR, Dickerson RE. Structure of a B-DNA dodecamer. III. Geometry of hydration. J Mol Biol. 1981 Sep 25;151(3):535–556. [PubMed]
  • Ellison MJ, Kelleher RJ, 3rd, Wang AH, Habener JF, 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. [PMC free article] [PubMed]
  • Ellison MJ, Feigon J, Kelleher RJ, 3rd, Wang AH, Habener JF, 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. [PubMed]
  • Feigon J, Wang AH, van der Marel GA, van Boom JH, Rich A. Z-DNA forms without an alternating purine-pyrimidine sequence in solution. Science. 1985 Oct 4;230(4721):82–84. [PubMed]
  • Greaves DR, Patient RK, Lilley DM. Facile cruciform formation by an (A-T)34 sequence from a Xenopus globin gene. J Mol Biol. 1985 Oct 5;185(3):461–478. [PubMed]
  • Hagen FK, Zarling DA, Jovin TM. Electron microscopy of SV40 DNA cross-linked by anti-Z DNA IgG. EMBO J. 1985 Mar;4(3):837–844. [PMC free article] [PubMed]
  • Haniford DB, Pulleyblank DE. 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. [PubMed]
  • Haniford DB, Pulleyblank DE. 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. [PMC free article] [PubMed]
  • Haschemeyer AE, 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. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Johnston BH, Rich A. Chemical probes of DNA conformation: detection of Z-DNA at nucleotide resolution. Cell. 1985 Oct;42(3):713–724. [PubMed]
  • Jovin TM, McIntosh LP, Arndt-Jovin DJ, Zarling DA, Robert-Nicoud M, van de Sande JH, Jorgenson KF, Eckstein F. Left-handed DNA: from synthetic polymers to chromosomes. J Biomol Struct Dyn. 1983 Oct;1(1):21–57. [PubMed]
  • Kmiec EB, Holloman WK. Homologous pairing of DNA molecules by Ustilago rec1 protein is promoted by sequences of Z-DNA. Cell. 1986 Feb 28;44(4):545–554. [PubMed]
  • Kmiec EB, Angelides KJ, Holloman WK. Left-handed DNA and the synaptic pairing reaction promoted by Ustilago rec1 protein. Cell. 1985 Jan;40(1):139–145. [PubMed]
  • Konopka AK, Reiter J, Jung M, Zarling DA, Jovin TM. 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. [PMC free article] [PubMed]
  • Lafer EM, 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. [PMC free article] [PubMed]
  • Miller FD, Jorgenson KF, Winkfein RJ, van de Sande JH, Zarling DA, Stockton J, Rattner JB. Natural occurrence of left-handed (Z) regions in PM2 DNA. J Biomol Struct Dyn. 1983 Dec;1(3):611–620. [PubMed]
  • 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. [PubMed]
  • Nordheim A, Lafer EM, Peck LJ, Wang JC, Stollar BD, 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. [PubMed]
  • 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. [PubMed]
  • Peck LJ, Wang JC. Energetics of B-to-Z transition in DNA. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6206–6210. [PMC free article] [PubMed]
  • Pohl FM, Jovin TM. 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. [PubMed]
  • Pulleyblank DE, Shure M, Tang D, Vinograd J, Vosberg HP. 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. [PMC free article] [PubMed]
  • Pulleyblank DE, Haniford DB, Morgan AR. A structural basis for S1 nuclease sensitivity of double-stranded DNA. Cell. 1985 Aug;42(1):271–280. [PubMed]
  • Revet B, Zarling DA, Jovin TM, 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. [PMC free article] [PubMed]
  • Rich A, Nordheim A, Wang AH. The chemistry and biology of left-handed Z-DNA. Annu Rev Biochem. 1984;53:791–846. [PubMed]
  • Singleton CK, Klysik J, Stirdivant SM, Wells RD. Left-handed Z-DNA is induced by supercoiling in physiological ionic conditions. Nature. 1982 Sep 23;299(5881):312–316. [PubMed]
  • Stockton JF, Miller FD, Jorgenson KF, Zarling DA, Morgan AR, Rattner JB, van de Sande JH. Left-handed Z-DNA regions are present in negatively supercoiled bacteriophage PM2 DNA. EMBO J. 1983;2(12):2123–2128. [PMC free article] [PubMed]
  • Vologodskii AV, Frank-Kamenetskii MD. Left-handed Z form in superhelical DNA: a theoretical study. J Biomol Struct Dyn. 1984 Jun;1(6):1325–1333. [PubMed]
  • Wang AH, Quigley GJ, Kolpak FJ, Crawford JL, van Boom JH, 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. [PubMed]
  • Wang AJ, Quigley GJ, Kolpak FJ, van der Marel G, van Boom JH, Rich A. Left-handed double helical DNA: variations in the backbone conformation. Science. 1981 Jan 9;211(4478):171–176. [PubMed]
  • Wang AH, Gessner RV, van der Marel GA, van Boom JH, 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. [PMC free article] [PubMed]
  • Zarling DA, Arndt-Jovin DJ, Robert-Nicoud M, McIntosh LP, Thomae R, Jovin TM. Immunoglobulin recognition of synthetic and natural left-handed Z DNA conformations and sequences. J Mol Biol. 1984 Jul 5;176(3):369–415. [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...