Unusual DNA Structures and Gene Regulation
Left-handed Z-DNA, cruciforms, purine·pyrimidine (pur·pyr) sequences, and bent DNA have been studied with supercoiled recombinant plasmids, restriction fragments, and DNA polymers. Different types of sequences of cellular and viral origin as well as synthetic polymers and plasmid inserts have been investigated.
Left-handed Z-DNA is stabilized by negative supercoiling for a variety of suitable sequences. Strictly alternating purine-pyrimidine sequences are neither necessary nor sufficient for Z-DNA formation. The junctions between right-handed B and left-handed Z helices contain few, if any, nonpaired bases. Consecutive AT pairs can adopt left-handed Z conformations.
DNA cruciforms are stabilized by negative supercoiling at inverted repeat sequences. The influence of salts, temperature, and stem length indicates a sensitive interrelationship between these factors for cruciform stability.
Segments of recombinant plasmids containing pur·pyr sequences adopt unusual helical conformations under the influence of negative supercoiling. This feature is recognized and specifically cleaved by Sl nuclease. The major late promoter of adenovirus exhibits this property at the TATA box. A variety of other studies led to the conclusion that the B-helix deformation was not due to a previously recognized DNA conformation. Furthermore, the direct repeat sequences at the cleavage-packaging signal of herpes simplex virus type 1 adopts a novel DNA structure under the influence of negative supercoiling. The properties of this direct repeat have been previously unrecognized with any other system. This DNA (anisomorphic DNA) has different conformations in the complementary strands, which give rise to an aberrant DNA structure in the center of the direct repeat sequences.
Bent DNA occurs in fragments of kinetoplast DNA from Crithidia as well as other trypanosomes. Most fragments contain numerous runs of 4 to 6 A’s which are spaced with a periodicity of 1 per helical repeat.
The chemical and biological properties of these unusual DNA conformations are described.
KeywordsHerpes Simplex Virus Type Negative Supercoiling Direct Repeat Sequence Major Late Promoter Nuclease Sensitivity
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- 4.C.K. Singleton in: Cell Proliferation: Recent Advances (Leffert, H.L. and Boynton, A.L., eds., 1984), Academic Press, New York.Google Scholar
- 8.R.D. Wells, B.F. Erlanger, H.B. Gray, L.H. Hanau, T.M. Jovin, M.W. Kilpatrick, J. Klysik, J.E. Larson, J.C. Martin, J.J. Miglietta, C.K. Singleton, S.M. Stirdivant, C.M. Veneziale, R.M. Wartell, C.F. Wei, W. Zacharias, and D. Zarling, Gene Expression, UCLA Symp. Mol. Cell. Biol. 8, 3–18 (1983).Google Scholar
- 19.H.R. Bergen, III, M.J. Losman, T.R. O’Connor, W. Zacharias, J.E. Larson, R.D. Wells, and W.J. Koopman, J. Immun., submitted 1986.Google Scholar
- 21.G. Galazka, E. Palacek, R.D. Wells, and J. Klysik, J. Biol. Chem. in press, 1986.Google Scholar
- 23.T.R. O’Connor, D.S. Kang, and R.D. Wells, J. Biol. Chem., in the press 1986.Google Scholar
- 41.T.R. O’Connor, D.S. Kang, and R.D. Wells, J. Biol. Chem., in the press (1986).Google Scholar
- 44.R.D. Wells, J.E. Larson, R.C. Grant, B.E. Shortle, and Cantor, C.R., J. Mol. Biol. 54, 465-497.Google Scholar
- 49.D. Dybvig, D.D. Clark, G. Aliperti, and M.J. Schlesinger, Nucl. Acids Res. 11, 8495-8505.Google Scholar
- 54.A. J. Nahmias. in: Viruses, Evolution and Cancer (E. Kurstak and K. Maramorosch, eds.) 605–634, Academic Press, New York (1980).Google Scholar
- 55.P.G. Spear and B. Roizman in: DNA Tumor Viruses (J. Tooze, ed.) 615-746, Cold Spring Harbor (1980).Google Scholar
- 64.F. Wohlrab, M.J. McLean, and R.D. Wells, submitted (1986).Google Scholar
- 67.E. Seising, R.D. Wells, C.J. Alden, and S. Arnott, J. Biol. Chem., 254, 5555–5561 (1979).Google Scholar
- 70.F. Wohlrab and R.D. Wells, Gene Amplification and Analysis, Vol. 5, in the press (1986).Google Scholar