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. 1998 Jun 1;26(11):2694–2701. doi: 10.1093/nar/26.11.2694

Thermodynamics of internal C.T mismatches in DNA.

H T Allawi 1, J SantaLucia Jr 1
PMCID: PMC147606  PMID: 9592156

Abstract

Thermodynamics of 23 oligonucleotides with internal single C.T mismatches were obtained by measuring UV absorbance as a function of temperature. Results from these 23 duplexes were combined with three measurements from the literature to derive nearest-neighbor thermodynamic parameters for seven linearly independent trimer sequences with internal C.T mismatches. The data show that the nearest-neighbor model is adequate for predicting thermodynamics of oligonucleotides with internal C.T with average deviations for Delta G degrees37, Delta H degrees, Delta S degrees and T m of 6.4%, 9.9%, 10.6%, and 1.9 degreesC respectively. C.T mismatches destabilize the duplex in all sequence contexts. The thermodynamic contribution of C. T mismatches to duplex stability varies weakly depending on the orientation of the mismatch and its context and ranges from +1.02 kcal/mol for GCG/CTC and CCG/GTC to +1.95 kcal/mol for TCC/ATG.

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Selected References

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  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. Allawi H. T., SantaLucia J., Jr Nearest neighbor thermodynamic parameters for internal G.A mismatches in DNA. Biochemistry. 1998 Feb 24;37(8):2170–2179. doi: 10.1021/bi9724873. [DOI] [PubMed] [Google Scholar]
  3. Allawi H. T., SantaLucia J., Jr Thermodynamics and NMR of internal G.T mismatches in DNA. Biochemistry. 1997 Aug 26;36(34):10581–10594. doi: 10.1021/bi962590c. [DOI] [PubMed] [Google Scholar]
  4. Bhattacharyya A., Lilley D. M. Single base mismatches in DNA. Long- and short-range structure probed by analysis of axis trajectory and local chemical reactivity. J Mol Biol. 1989 Oct 20;209(4):583–597. doi: 10.1016/0022-2836(89)90596-2. [DOI] [PubMed] [Google Scholar]
  5. Bhaumik S. R., Chary K. V., Govil G., Liu K., Miles H. T. Homopurine and homopyrimidine strands complementary in parallel orientation form an antiparallel duplex at neutral pH with A-C, G-T, and T-C mismatched base pairs. Biopolymers. 1997 Jun;41(7):773–784. doi: 10.1002/(SICI)1097-0282(199706)41:7<773::AID-BIP6>3.0.CO;2-M. [DOI] [PubMed] [Google Scholar]
  6. Borer P. N., Dengler B., Tinoco I., Jr, Uhlenbeck O. C. Stability of ribonucleic acid double-stranded helices. J Mol Biol. 1974 Jul 15;86(4):843–853. doi: 10.1016/0022-2836(74)90357-x. [DOI] [PubMed] [Google Scholar]
  7. Boulard Y., Cognet J. A., Fazakerley G. V. Solution structure as a function of pH of two central mismatches, C . T and C . C, in the 29 to 39 K-ras gene sequence, by nuclear magnetic resonance and molecular dynamics. J Mol Biol. 1997 May 2;268(2):331–347. doi: 10.1006/jmbi.1997.0975. [DOI] [PubMed] [Google Scholar]
  8. Chee M., Yang R., Hubbell E., Berno A., Huang X. C., Stern D., Winkler J., Lockhart D. J., Morris M. S., Fodor S. P. Accessing genetic information with high-density DNA arrays. Science. 1996 Oct 25;274(5287):610–614. doi: 10.1126/science.274.5287.610. [DOI] [PubMed] [Google Scholar]
  9. Doktycz M. J., Goldstein R. F., Paner T. M., Gallo F. J., Benight A. S. Studies of DNA dumbbells. I. Melting curves of 17 DNA dumbbells with different duplex stem sequences linked by T4 endloops: evaluation of the nearest-neighbor stacking interactions in DNA. Biopolymers. 1992 Jul;32(7):849–864. doi: 10.1002/bip.360320712. [DOI] [PubMed] [Google Scholar]
  10. Elkins T. E., Brown D. Ethical concerns and future directions in maternal screening for Down syndrome. Womens Health Issues. 1995 Spring;5(1):15–20. doi: 10.1016/1049-3867(94)00055-U. [DOI] [PubMed] [Google Scholar]
  11. Fodor S. P., Rava R. P., Huang X. C., Pease A. C., Holmes C. P., Adams C. L. Multiplexed biochemical assays with biological chips. Nature. 1993 Aug 5;364(6437):555–556. doi: 10.1038/364555a0. [DOI] [PubMed] [Google Scholar]
  12. Gaffney B. L., Jones R. A. Thermodynamic comparison of the base pairs formed by the carcinogenic lesion O6-methylguanine with reference both to Watson-Crick pairs and to mismatched pairs. Biochemistry. 1989 Jul 11;28(14):5881–5889. doi: 10.1021/bi00440a026. [DOI] [PubMed] [Google Scholar]
  13. Goodman M. F., Creighton S., Bloom L. B., Petruska J. Biochemical basis of DNA replication fidelity. Crit Rev Biochem Mol Biol. 1993;28(2):83–126. doi: 10.3109/10409239309086792. [DOI] [PubMed] [Google Scholar]
  14. Gray D. M. Derivation of nearest-neighbor properties from data on nucleic acid oligomers. I. Simple sets of independent sequences and the influence of absent nearest neighbors. Biopolymers. 1997 Dec;42(7):783–793. doi: 10.1002/(sici)1097-0282(199712)42:7<783::aid-bip4>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  15. Holbrook S. R., Cheong C., Tinoco I., Jr, Kim S. H. Crystal structure of an RNA double helix incorporating a track of non-Watson-Crick base pairs. Nature. 1991 Oct 10;353(6344):579–581. doi: 10.1038/353579a0. [DOI] [PubMed] [Google Scholar]
  16. Ikoku A. S., Hearst J. E. Identification of a structural hairpin in the filamentous chimeric phage M13Gori1. J Mol Biol. 1981 Sep 15;151(2):245–259. doi: 10.1016/0022-2836(81)90514-3. [DOI] [PubMed] [Google Scholar]
  17. Ke S. H., Wartell R. M. The thermal stability of DNA fragments with tandem mismatches at a d(CXYG).d(CY'X'G) site. Nucleic Acids Res. 1996 Feb 15;24(4):707–712. doi: 10.1093/nar/24.4.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kierzek R., Caruthers M. H., Longfellow C. E., Swinton D., Turner D. H., Freier S. M. Polymer-supported RNA synthesis and its application to test the nearest-neighbor model for duplex stability. Biochemistry. 1986 Dec 2;25(24):7840–7846. doi: 10.1021/bi00372a009. [DOI] [PubMed] [Google Scholar]
  19. Marky L. A., Breslauer K. J. Calculating thermodynamic data for transitions of any molecularity from equilibrium melting curves. Biopolymers. 1987 Sep;26(9):1601–1620. doi: 10.1002/bip.360260911. [DOI] [PubMed] [Google Scholar]
  20. McDowell J. A., Turner D. H. Investigation of the structural basis for thermodynamic stabilities of tandem GU mismatches: solution structure of (rGAGGUCUC)2 by two-dimensional NMR and simulated annealing. Biochemistry. 1996 Nov 12;35(45):14077–14089. doi: 10.1021/bi9615710. [DOI] [PubMed] [Google Scholar]
  21. Morozov SYu, Chernov B. K., Merits A., Blinov V. M. Computer-assisted predictions of the secondary structure in the plant virus single-stranded DNA genome. J Biomol Struct Dyn. 1994 Feb;11(4):837–847. doi: 10.1080/07391102.1994.10508036. [DOI] [PubMed] [Google Scholar]
  22. Ozawa K., Kurtzman G., Young N. Replication of the B19 parvovirus in human bone marrow cell cultures. Science. 1986 Aug 22;233(4766):883–886. doi: 10.1126/science.3738514. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Pease A. C., Solas D., Sullivan E. J., Cronin M. T., Holmes C. P., Fodor S. P. Light-generated oligonucleotide arrays for rapid DNA sequence analysis. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5022–5026. doi: 10.1073/pnas.91.11.5022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Petersheim M., Turner D. H. Base-stacking and base-pairing contributions to helix stability: thermodynamics of double-helix formation with CCGG, CCGGp, CCGGAp, ACCGGp, CCGGUp, and ACCGGUp. Biochemistry. 1983 Jan 18;22(2):256–263. doi: 10.1021/bi00271a004. [DOI] [PubMed] [Google Scholar]
  26. Piotto M., Saudek V., Sklenár V. Gradient-tailored excitation for single-quantum NMR spectroscopy of aqueous solutions. J Biomol NMR. 1992 Nov;2(6):661–665. doi: 10.1007/BF02192855. [DOI] [PubMed] [Google Scholar]
  27. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  28. SantaLucia J., Jr A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics. Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1460–1465. doi: 10.1073/pnas.95.4.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. SantaLucia J., Jr, Allawi H. T., Seneviratne P. A. Improved nearest-neighbor parameters for predicting DNA duplex stability. Biochemistry. 1996 Mar 19;35(11):3555–3562. doi: 10.1021/bi951907q. [DOI] [PubMed] [Google Scholar]
  30. SantaLucia J., Jr, Kierzek R., Turner D. H. Stabilities of consecutive A.C, C.C, G.G, U.C, and U.U mismatches in RNA internal loops: Evidence for stable hydrogen-bonded U.U and C.C.+ pairs. Biochemistry. 1991 Aug 20;30(33):8242–8251. doi: 10.1021/bi00247a021. [DOI] [PubMed] [Google Scholar]
  31. Sugimoto N., Nakano S., Katoh M., Matsumura A., Nakamuta H., Ohmichi T., Yoneyama M., Sasaki M. Thermodynamic parameters to predict stability of RNA/DNA hybrid duplexes. Biochemistry. 1995 Sep 5;34(35):11211–11216. doi: 10.1021/bi00035a029. [DOI] [PubMed] [Google Scholar]
  32. Sugimoto N., Nakano S., Yoneyama M., Honda K. Improved thermodynamic parameters and helix initiation factor to predict stability of DNA duplexes. Nucleic Acids Res. 1996 Nov 15;24(22):4501–4505. doi: 10.1093/nar/24.22.4501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Vologodskii A. V., Amirikyan B. R., Lyubchenko Y. L., Frank-Kamenetskii M. D. Allowance for heterogeneous stacking in the DNA helix-coil transition theory. J Biomol Struct Dyn. 1984 Aug;2(1):131–148. doi: 10.1080/07391102.1984.10507552. [DOI] [PubMed] [Google Scholar]

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