Abstract
Mutational pathways rely on introducing changes in the DNA double helix. This may be achieved by the incorporation of a noncomplementary base on replication or during genetic recombination1,2, leading to substitution mutation. In vivo studies3–7 have shown that most combinations of base-pair mismatches can be accommodated in the DNA double helix, albeit with varying efficiencies. Fidelity of replication requires the recognition and excision of mismatched bases by proofreading enzymes and post-replicative mismatch repair systems. Rates of excision vary with the type of mismatch and there is some evidence that these are influenced by the nature of the neighbouring sequences8,9. However, there is little experimental information about the molecular structure of mismatches and their effect on the DNA double helix. We have recently determined the crystal structures of several DNA fragments with guanine o thymine and adenine o guanine mismatches in a full turn of a B-DNA helix and now report the nature of the base pairing between adenine and cytosine in an isomorphous fragment. The base pair found in the present study is novel and we believe has not previously been demonstrated. Our results suggest that the enzymatic recognition of mismatches is likely to occur at the level of the base pairs and that the efficiency of repair can be correlated with structural features.
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
Radding, C. M. A Rev. Biochem. 47, 847–880 (1978).
Loeb, A. L. & Kunkel, T. A. A. Rev. Biochem. 51, 429–457 (1982).
Lu, A. L., Welsh, K., Clark, S., Su, S. S. & Moldrich, P. Cold Spring Harb. Symp quant. Biol. 49, 589–596 (1984).
Kramer, B., Kramer, W. & Fritz, H. J. Cell 38, 879–887 (1985).
Dohet, C., Wagner, R. & Radman, M. Proc. natn. Acad. Sci. U.S.A. 82, 503–505 (1985).
Claverys, S. J. P., Mejan, V., Gasc, A. M. & Siccard, A. M. Proc. natn. Acad. Sci. U.S.A. 80, 5956–5960 (1983).
White, J. H., Lusnak, K. & Fogel, S. Nature 315, 350–352 (1985).
Fersht, A. R., Knill-Jones, J. W. & Tsui, W.-C. J molec. Biol. 156, 37–51 (1982).
Topal, M. D., DiGuiseppi, S. R. & Sinhai, N. K. J. biol. Chem. 255, 11717–11724 (1980).
Crick, F. H. C. J. molec. Biol. 19, 548–555 (1966).
Watson, J. D. & Crick, F. H. C. Nature 171, 694–967 (1953).
Drake, J. W. Molecular Basis of Mutations (Holden-Day, San Francisco, 1970).
Topal, M. D. & Fresco, J. R. Nature 265, 285–189 (1976).
Patel, D. J., Kozlowski, S. A., Ikuta, S. & Itakura, K. Biochemistry 23, 3218–3226 (1984).
Kennard, O. J. biomolec. Struct. Dyn. 3, 205–225 (1985).
Brown, T., Hunter, W. N., Kneale, G. & Kennard, O. Proc. natn. Acad. Sci. U.S.A. (in the press).
Wing, R. et al. Nature 287, 755–758 (1980).
Hendrickson, W.A. & Konnert, J. H. in Biomolecular Structure, Conformation, Function and Evolution Vol. 1 (ed. Srinivasan, R.) 43–57 (Pergamon, Oxford, 1981).
Westhof, E., Dumas, P. & Moras, D. J. molec. Biol. 184, 119–145 (1985).
Saenger, W. Principles of Nucleic Acid Structure (Springer, New York, 1984).
Taylor, R. & Kennard, O. J. molec. Struct. 78, 1028 (1982).
Rich, A., Davies, D. R., Crick, F. H. C. & Watson, J. D. J. molec. Biol. 3, 71–86 (1961).
Churprina, V. P. & Poltev, V. I. Nucleic Acids Res. 13, 141–152 (1985).
Arnott, S. & Hukins, D. W. I. Biochem. biophys. Res. Commun. 47, 1504–1509 (1972).
Brdwn, T., Kennard, O., Kneale, G. & Rabinovich, D. Nature 315, 604–606 (1985).
Kneale, G., Brown, T., Kennard, O. & Rabinovich, D. J. molec. Biol 186, 805–814 (1985).
Brown, T., Kneale, G., Hunter, W. N. & Kennard, O. Nucleic Acids Res. (in the press).
Ho, P. S. et al. EMBO J. 4, 3617–3623 (1985).
Tibanyenda, N. et al Eur. J. Biochem. 139, 19–25 (1983).
Patel, D. J., Koslowski, S. A., Ikuta, S. & Itakura, K. Fedn Proc. 43, 2663–2670 (1984).
Aboul-ela, F., Koh, D., Tinoco, F. Jr & Martin, F. H. Nucleic Acids Res. 13, 4811–4824 (1985).
Salisbury, S. & Anand, N. N. JCS chem. Commun. 985–986 (1985).
Seeman, N. C., Rosenberg, J. M. & Rich, A. Proc. natn. Acad. Sci. U.S.A. 73, 804–808 (1976).
Rein, R., Shibata, M., Gardino-Juarez, R. & Keiber-Emmons, T. Structure and Dynamics of Nucleic Acids and Proteins (eds Clementi, E. & Sarma, R.) 269–288 (Adenine, New York, 1983).
Dickerson, R. E. J. molec. Biol. 153, 410–441 (1983).
Shakked, Z. & Kennard, O. in Biological Macromolecules and Assemblies Vol. 2 (eds McPherson, A. & Jurnak, F.) 1–36 (Wiley, New York, 1985).
Haran, T. E., Berkovitch-Yellin, Z. & Shakked, Z. J. biomolec. Struct. Dyn. 2, 397–412 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hunter, W., Brown, T., Anand, N. et al. Structure of an adenine˙cytosine base pair in DNA and its implications for mismatch repair. Nature 320, 552–555 (1986). https://doi.org/10.1038/320552a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/320552a0
This article is cited by
-
Structural insights into mutagenicity of anticancer nucleoside analog cytarabine during replication by DNA polymerase η
Scientific Reports (2019)
-
Smoking gun for a rare mutation mechanism
Nature (2018)
-
Proton Transfer Accounting for Anomalous Collision-Induced Dissociation of Proton-Bound Hoogsteen Base Pair of Cytosine and Guanine
Journal of the American Society for Mass Spectrometry (2018)
-
N3 and O2 Protonated Conformers of the Cytosine Mononucleotides Coexist in the Gas Phase
Journal of the American Society for Mass Spectrometry (2017)
-
Theoretical exploration of gas-phase conformers of proton-bound non-covalent heterodimers of guanine and cytosine rare tautomers: structures and energies
Theoretical Chemistry Accounts (2017)
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.
