DNA A-tracts have been defined as four or more consecutive A.T base pairs without a TpA step. When inserted in phase with the DNA helical repeat, bending is manifested macroscopically as anomalous migration on polyacrylamide gels, first observed >20 years ago. An unsolved conundrum is why DNA containing in-phase A-tract repeats of A(4)T(4) are bent, whereas T(4)A(4) is straight. We have determined the solution structures of the DNA duplexes formed by d(GCAAAATTTTGC) [A4T4] and d(CGTTTTAAAACG) [T4A4] with NH(4)(+) counterions by using NMR spectroscopy, including refinement with residual dipolar couplings. Analysis of the structures shows that the ApT step has a large negative roll, resulting in a local bend toward the minor groove, whereas the TpA step has a positive roll and locally bends toward the major groove. For A4T4, this bend is nearly in phase with bends at the two A-tract junctions, resulting in an overall bend toward the minor groove of the A-tract, whereas for T4A4, the bends oppose each other, resulting in a relatively straight helix. NMR-based structural modeling of d(CAAAATTTTG)(15) and d(GTTTTAAAAC)(15) reveals that the former forms a left-handed superhelix with a diameter of approximately 110 A and pitch of 80 A, similar to DNA in the nucleosome, whereas the latter has a gentle writhe with a pitch of >250 A and diameter of approximately 50 A. Results of gel electrophoretic mobility studies are consistent with the higher-order structure of the DNA and furthermore depend on the nature of the monovalent cation present in the running buffer.

National Center for Biomolecular Research NMR Laboratory Faculty of Science Masaryk University Kotlárská 2 CZ 611 37 Brno Czech Republic

Zobrazit více v PubMed

Marini, J. C., Levene, S. D., Crothers, D. M. & Englund, P. T. (1982) Proc. Natl. Acad. Sci. USA 79 PubMed PMC

Wu, H.-M. & Crothers, D. M. (1984) Nature 308 PubMed

Hagerman, P. J. (1990) Annu. Rev. Biochem. 59 PubMed

Crothers, D. M. & Shakked, Z. (1999) in Oxford Handbook of Nucleic Acid Structure, ed. Neidle, S. (Oxford Univ. Press, Oxford), pp. 455–470.

Trifonov, E. N. & Sussman, J. L. (1980) Proc. Natl. Acad. Sci. USA 77 PubMed PMC

Ulanovsky, L. E. & Trifonov, E. N. (1987) Nature 326 PubMed

Bolshoy, A., McNamara, P., Harrington, R. E. & Trifonov, E. N. (1991) Proc. Natl. Acad. Sci. USA 88 PubMed PMC

De Santis, P., Palleschi, A., Savino, M. & Scipioni, A. (1990) Biochemistry 29 PubMed

Koo, H.-S., Wu, H.-M. & Crothers, D. M. (1986) Nature 320 PubMed

Koo, H. S. & Crothers, D. M. (1988) Proc. Natl. Acad. Sci. USA 85 PubMed PMC

Haran, T. E., Hahn, J. D. & Crothers, D. M. (1994) J. Mol. Biol. 244 PubMed

Hud, N. V. & Plavec, J. (2003) Biopolymers 69 PubMed

DiGabriele, A. D. & Steitz, T. A. (1993) J. Mol. Biol. 231 PubMed

DiGabriele, A. D., Sanderson, M. R. & Steitz, T. A. (1989) Proc. Natl. Acad. Sci. USA 86 PubMed PMC

Dickerson, R. E., Goodsell, D. S. & Neidle, S. (1994) Proc. Natl. Acad. Sci. USA 91 PubMed PMC

Dlakic, M., Park, K., Griffith, J. D., Harvey, S. C. & Harrington, R. E. (1996) J. Biol. Chem. 271 PubMed

Nelson, H. C., Finch, J. T., Luisi, B. F. & Klug, A. (1987) Nature 330 PubMed

Dickerson, R. E., Goodsell, D. & Kopka, M. L. (1996) J. Mol. Biol. 256 PubMed

Tjandra, N. & Bax, A. (1997) Science 278 PubMed

Tjandra, N., Tate, S., Ono, A., Kainosho, M. & Bax, A. (2000) J. Am. Chem. Soc. 122

MacDonald, D., Herbert, K., Zhang, X. L., Polgruto, T. & Lu, P. (2001) J. Mol. Biol. 306 PubMed

Barbic, A., Zimmer, D. P. & Crothers, D. M. (2003) Proc. Natl. Acad. Sci. USA 100 PubMed PMC

Crothers, D. M. (1994) Science 266 PubMed

Hagerman, P. J. (1988) in Unusual DNA Structures, eds. Wells, R. D. & Harvey, S. C. (Springer, New York), pp. 225–236.

Hagerman, P. J. (1986) Nature 321 PubMed

Richmond, T. J. & Davey, C. A. (2003) Nature 423 PubMed

Masse, J., Bortmann, P., Dieckmann, T. & Feigon, J. (1998) Nucleic Acids Res. 26 PubMed PMC

Kolk, M. H., Wijmenga, S. S., Heus, H. A. & Hilbers, C. W. (1998) J. Biomol. NMR 12

Legault, P., Jucker, F. M. & Pardi, A. (1995) FEBS Lett. 362 PubMed

Trantirek, L., Stefl, R., Masse, J. E., Feigon, J. & Sklenář, V. (2002) J. Biolmol. NMR 23 PubMed

Hansen, M. R., Mueller, L. & Pardi, A. (1998) Nat. Struct. Biol. 5 PubMed

Case, D. A., Pearlman, D. A., Caldwell, J. W., Cheatham, T. E. I., Wang, J., Ross, W. S., Simmerling, C. L., Darden, T. A., Merz, K. M., Stanton, R. V.,

Cornell, W. D., Cieplak, P., Bayly, C. I., Gould, I. R., Merz, K. M. J., Ferguson, D. M., Spellmeyer, D. C., Fox, T., Caldwell, J. W. & Kollman, P. A. (1995) J. Am. Chem. Soc. 117

Padrta, P., Stefl, R., Králík, L., Zídek, L. & Sklenář, V. (2002) J. Biomol. NMR 24 PubMed

Bashford, D. & Case, D. A. (2000) Annu. Rev. Phys. Chem. 51 PubMed

Tsui, V., Zhu, L., Huang, T.-H., Wright, P. E. & Case, D. A. (2000) J. Biomol. NMR 16 PubMed

Lu, X. J., Shakked, Z. & Olson, W. K. (2000) J. Mol. Biol. 300 PubMed

Olson, W. K., Bansal, M., Burley, S. K., Dickerson, R. E., Gerstein, M., Harvey, S. C., Heinemann, U., Lu, X. J., Neidle, S., Shakked, Z., PubMed

Strahs, D. & Schlick, T. (2000) J. Mol. Biol. 301 PubMed

Hud, N. V., Schultze, P. & Feigon, J. (1998) J. Am. Chem. Soc. 120

Mack, D. R., Chiu, T. K. & Dickerson, R. E. (2001) J. Mol. Biol. 312 PubMed

Young, M. A., Ravishanker, G., Beveridge, D. L. & Berman, H. M. (1995) Biophys. J. 68 PubMed PMC

Boisbouvier, J., Delaglio, F. & Bax, A. (2003) Proc. Natl. Acad. Sci. USA 100 PubMed PMC

Diekmann, S., Mazzarelli, J. M., McLaughlin, L. W., von Kitzing, E. & Travers, A. A. (1992) J. Mol. Biol. 225 PubMed

Jerkovic, B. & Bolton, P. H. (2000) Biochemistry 39 PubMed

Diekmann, S. (1987) Nucleic Acids Res. 15 PubMed PMC

Drew, H. R. & Dickerson, R. E. (1981) J. Mol. Biol. 151 PubMed

Drak, J. & Crothers, D. M. (1991) Proc. Natl. Acad. Sci. USA 88 PubMed PMC

Tereshko, V., Minasov, G. & Egli, M. (1999) J. Am. Chem. Soc. 121

Woods, K. K., McFail-Isom, L., Sines, C. C., Howerton, S. B., Stephens, R. K. & Williams, L. D. (2000) J. Am. Chem. Soc. 122

Young, M. A., Jayaram, B. & Beveridge, D. L. (1997) J. Am. Chem. Soc. 119

Stellwagen, N. C., Magnusdottir, S., Gelfi, C. & Righetti, P. G. (2001) J. Mol. Biol. 305 PubMed

Hud, N. V., Sklenář, V. & Feigon, J. (1999) J. Mol. Biol. 286 PubMed

Denisov, V. P. & Halle, B. (2000) Proc. Natl. Acad. Sci. USA 97 PubMed PMC

Stefl, R. & Koca, J. (2000) J. Am. Chem. Soc. 122

Lavery, R. & Sklenář, H. (1988) J. Biomol. Struct. Dyn. 6 PubMed

Edwards, K. J., Brown, D. G., Spink, N., Skelly, J. V. & Neidle, S. (1992) J. Mol. Biol. 226 PubMed

Sequence-Dependent Shape and Stiffness of DNA and RNA Double Helices: Hexanucleotide Scale and Beyond

Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning

Toward Improved Description of DNA Backbone: Revisiting Epsilon and Zeta Torsion Force Field Parameters

A measure of bending in nucleic acids structures applied to A-tract DNA

Zobrazit více v PubMed

PDB
1RVH, 1RVI