Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1990 Oct 11;18(19):5617–5623. doi: 10.1093/nar/18.19.5617

Structural and thermodynamic studies on the adenine.guanine mismatch in B-DNA.

G A Leonard 1, E D Booth 1, T Brown 1
PMCID: PMC332291  PMID: 2216754

Abstract

The structure of the synthetic dodecamer d(CGCAAATTGGCG) has been shown by single crystal X-ray diffraction methods to be that of a B-DNA helix containing two A(anti).G(syn) base pairs. The refinement, based on data to a resolution of 2.25 A shows that the mismatch base pairs are held together by two hydrogen bonds. The syn-conformation of the guanine base of the mismatch is stabilised by hydrogen bonding to a network of solvent molecules in both the major and minor grooves. A pH-dependent ultraviolet melting study indicates that the duplex is stabilised by protonation, suggesting that the bases of the A.G mispair are present in their most common tautomeric forms and that the N(1)-atom of adenine is protonated. The structure refinement shows that there is some disorder in the sugar-phosphate backbone.

Full text

PDF
5617

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aboul-ela F., Koh D., Tinoco I., Jr, Martin F. H. Base-base mismatches. Thermodynamics of double helix formation for dCA3XA3G + dCT3YT3G (X, Y = A,C,G,T). Nucleic Acids Res. 1985 Jul 11;13(13):4811–4824. doi: 10.1093/nar/13.13.4811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown T., Hunter W. N., Kneale G., Kennard O. Molecular structure of the G.A base pair in DNA and its implications for the mechanism of transversion mutations. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2402–2406. doi: 10.1073/pnas.83.8.2402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown T., Leonard G. A., Booth E. D., Chambers J. Crystal structure and stability of a DNA duplex containing A(anti).G(syn) base-pairs. J Mol Biol. 1989 May 20;207(2):455–457. doi: 10.1016/0022-2836(89)90268-4. [DOI] [PubMed] [Google Scholar]
  4. Brown T., Leonard G. A., Booth E. D., Kneale G. Influence of pH on the conformation and stability of mismatch base-pairs in DNA. J Mol Biol. 1990 Apr 5;212(3):437–440. doi: 10.1016/0022-2836(90)90320-L. [DOI] [PubMed] [Google Scholar]
  5. Coll M., Frederick C. A., Wang A. H., Rich A. A bifurcated hydrogen-bonded conformation in the d(A.T) base pairs of the DNA dodecamer d(CGCAAATTTGCG) and its complex with distamycin. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8385–8389. doi: 10.1073/pnas.84.23.8385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Corfield P. W., Hunter W. N., Brown T., Robinson P., Kennard O. Inosine.adenine base pairs in a B-DNA duplex. Nucleic Acids Res. 1987 Oct 12;15(19):7935–7949. doi: 10.1093/nar/15.19.7935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fersht A. R., Knill-Jones J. W., Tsui W. C. Kinetic basis of spontaneous mutation. Misinsertion frequencies, proofreading specificities and cost of proofreading by DNA polymerases of Escherichia coli. J Mol Biol. 1982 Mar 25;156(1):37–51. doi: 10.1016/0022-2836(82)90457-0. [DOI] [PubMed] [Google Scholar]
  8. Frederick C. A., Quigley G. J., van der Marel G. A., van Boom J. H., Wang A. H., Rich A. Methylation of the EcoRI recognition site does not alter DNA conformation: the crystal structure of d(CGCGAm6ATTCGCG) at 2.0-A resolution. J Biol Chem. 1988 Nov 25;263(33):17872–17879. doi: 10.2210/pdb4dnb/pdb. [DOI] [PubMed] [Google Scholar]
  9. Gralla J., Crothers D. M. Free energy of imperfect nucleic acid helices. 3. Small internal loops resulting from mismatches. J Mol Biol. 1973 Aug 5;78(2):301–319. doi: 10.1016/0022-2836(73)90118-6. [DOI] [PubMed] [Google Scholar]
  10. Nelson H. C., Finch J. T., Luisi B. F., Klug A. The structure of an oligo(dA).oligo(dT) tract and its biological implications. Nature. 1987 Nov 19;330(6145):221–226. doi: 10.1038/330221a0. [DOI] [PubMed] [Google Scholar]
  11. Patel D. J., Kozlowski S. A., Ikuta S., Itakura K. Deoxyguanosine-deoxyadenosine pairing in the d(C-G-A-G-A-A-T-T-C-G-C-G) duplex: conformation and dynamics at and adjacent to the dG X dA mismatch site. Biochemistry. 1984 Jul 3;23(14):3207–3217. doi: 10.1021/bi00309a015. [DOI] [PubMed] [Google Scholar]
  12. Patel D. J., Kozlowski S. A., Ikuta S., Itakura K. Dynamics of DNA duplexes containing internal G.T, G.A, A.C, and T.C pairs: hydrogen exchange at and adjacent to mismatch sites. Fed Proc. 1984 Aug;43(11):2663–2670. [PubMed] [Google Scholar]
  13. Privé G. G., Heinemann U., Chandrasegaran S., Kan L. S., Kopka M. L., Dickerson R. E. Helix geometry, hydration, and G.A mismatch in a B-DNA decamer. Science. 1987 Oct 23;238(4826):498–504. doi: 10.1126/science.3310237. [DOI] [PubMed] [Google Scholar]
  14. Steitz T. A., Beese L., Freemont P. S., Friedman J. M., Sanderson M. R. Structural studies of Klenow fragment: an enzyme with two active sites. Cold Spring Harb Symp Quant Biol. 1987;52:465–471. doi: 10.1101/sqb.1987.052.01.053. [DOI] [PubMed] [Google Scholar]
  15. Tibanyenda N., De Bruin S. H., Haasnoot C. A., van der Marel G. A., van Boom J. H., Hilbers C. W. The effect of single base-pair mismatches on the duplex stability of d(T-A-T-T-A-A-T-A-T-C-A-A-G-T-T-G) . d(C-A-A-C-T-T-G-A-T-A-T-T-A-A-T-A). Eur J Biochem. 1984 Feb 15;139(1):19–27. doi: 10.1111/j.1432-1033.1984.tb07970.x. [DOI] [PubMed] [Google Scholar]
  16. Topal M. D., Fresco J. R. Complementary base pairing and the origin of substitution mutations. Nature. 1976 Sep 23;263(5575):285–289. doi: 10.1038/263285a0. [DOI] [PubMed] [Google Scholar]
  17. Wang A. H., Quigley G. J., Kolpak F. J., Crawford J. L., van Boom J. H., 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. doi: 10.1038/282680a0. [DOI] [PubMed] [Google Scholar]
  18. Werntges H., Steger G., Riesner D., Fritz H. J. Mismatches in DNA double strands: thermodynamic parameters and their correlation to repair efficiencies. Nucleic Acids Res. 1986 May 12;14(9):3773–3790. doi: 10.1093/nar/14.9.3773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Westhof E., Dumas P., Moras D. Crystallographic refinement of yeast aspartic acid transfer RNA. J Mol Biol. 1985 Jul 5;184(1):119–145. doi: 10.1016/0022-2836(85)90048-8. [DOI] [PubMed] [Google Scholar]
  20. Wing R., Drew H., Takano T., Broka C., Tanaka S., Itakura K., Dickerson R. E. Crystal structure analysis of a complete turn of B-DNA. Nature. 1980 Oct 23;287(5784):755–758. doi: 10.1038/287755a0. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES