Abstract
THE target sequence of the restriction enzyme NarI (GGCGCC) is a hot spot for the −2 frameshift mutagenesis (GGCGCC→GGCC) induced by the chemical carcinogens such as N-2-acetyl-aminofluorene1,2. Of the guanine residues, all of which show equal reactivity towards the carcinogen, only binding to the 3'-most proximal guanine within the Narl site is able to trigger the frameshift event3. We selected the non-palindromic dodecamer d(ACCGGCGCCACA), whose sequence corresponds to the most mutagenic Narl site in pBR322 DNA, for X-ray structure analysis. Its molecular structure determined at 2.8 å resolution reveals significant deviations from the structure of canonical B-form DNA, with partial opening of three G-C base pairs, high propeller twist values and sequence-dependent three-centred hydrogen bonds. This crystal structure shows a novel kind of packing in which helices are locked together by groove-backbone interactions. The partial opening of G-C base pairs is induced by interactions of phosphate anionic oxygen atoms with the amino group of cytosine bases. This provides a model for close approach of DNA molecules during biological processes, such as recombination.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Fuchs, R. P. P., Schwartz, N. & Daune, M. Nature 294, 657–659 (1981).
Koffel-Schwartz, N. et al. J. molec. Biol. 177, 33–51 (1984).
Burnouf, D., Koehl, P. & Fuchs, R. P. P. Proc. natn. Acad. Sci. U.S.A. 86, 4147–4151 (1989).
Wing, R. et al. Nature 287, 755–758 (1981).
Rabinovich, D., Haran, T., Eisenstein, M. & Shakked, Z. J. molec. Biol. 200, 151–161 (1988).
Yoon, C., Privé G., Goodsell, D. & Dickerson, R. Proc. natn. Acad. Sci. U.S.A. 85, 6332–6336 (1988).
Privé, G. et al. Science 238, 498–504 (1987).
Cruse, W. et al. J. molec. Biol. 192, 891–905 (1986).
Arnott, S. & Hukins, D. Biochem. biophys. Res. Commun. 47, 1504–1509 (1972).
Nelson, C., Finch, J., Luisi, B. & Klug, A. Nature 330, 221–226 (1987).
Coll, M., Frederick, C., Wang, A. & Rich, A. Proc. natn. Acad. Sci. U.S.A. 84, 8385–8389 (1987).
DiGabrielle, A., Sanderson, M. & Steitz, T. Proc. natn. Acad. Sci. U.S.A. 86, 1816–1820 (1989).
Aggarwal, A., Rodgers, D., Drottar, M., Ptashne, M., & Harrison, S. Science 249, 899–907 (1988).
Jordan, S. R. & Pabo, C. O. Science 242, 893–899 (1988).
Duckett, D. et al. Cell 55, 79–89 (1988).
Embo Workshop EMBO J. 8, 1–4 (1989).
Rabinovich, D. & Shakked, Z. Acta Crystallogr. A40, 195–200 (1984).
Fujinaga, M., Gros, P. & Van Gunsteren, W. F. J. appl. Crystallogr. 22, 1–8 (1989).
Westhof, E., Dumas, P. & Moras, D. J. molec. Biol. 184, 119–145 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Timsit, Y., Westhof, E., Fuchs, R. et al. Unusual helical packing in crystals of DNA bearing a mutation hot spot. Nature 341, 459–462 (1989). https://doi.org/10.1038/341459a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/341459a0
This article is cited by
-
The mutagenic properties of BrdUTP in a random mutagenesis process
Molecular Biology Reports (2008)
-
Determinants of repressor/operator recognition from the structure of the trp operator binding site
Nature (1994)
-
HMG has DNA wrapped up
Nature (1992)
-
Base-pairing shift in the major groove of (CA)n tracts by B-DNA crystal structures
Nature (1991)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.