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. 1991 Oct 15;88(20):9072–9076. doi: 10.1073/pnas.88.20.9072

Site-specific effect of thymine dimer formation on dAn.dTn tract bending and its biological implications.

C I Wang 1, J S Taylor 1
PMCID: PMC52654  PMID: 1924370

Abstract

dAn.dTn sequences, otherwise known as A tracts, are hotspots for cis-syn thymine dimer formation and deletion mutations induced by UV light. Such A tracts are also known to bend DNA, suggesting that some biological effects of UV light might be related to the distinctive structure and properties of cis-syn dimer-containing A tracts. To investigate the effect of thymine dimer formation on A-tract bending multimers of all possible dimer monoadducts of a dA6.dT6-containing decamer known to bend DNA were prepared along with multimers of a dimer-containing 21-mer of heterogeneous sequence. The characteristic anomalous electrophoretic behavior of the phased A-tract multimers was essentially abolished by dimer formation at the center of the A tract and was only slightly reduced by dimer formation at the ends. These effects are attributed to disruption of the A-tract structure at the site of the dimer, resulting in intact A tracts of reduced length and, hence, reduced bending. This model was suggested by the ability to formulate the estimated bend angles of the dimer-containing A tracts as approximately equal to the sum of the bend angles induced by the dimer and the remaining intact portion of the A tract. Contrary to a previous experimental study that concluded that the thymine dimer bends DNA by approximately 30 degrees, the dimer was determined to bend DNA by only approximately 7 degrees. Reduction of the bending of a DNA sequence by dimer formation may have a number of unpredicted and important biological consequences.

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Selected References

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

  1. Abagyan R. A., Mironov V. N., Chernov B. K., Chuprina V. P., Ulyanov A. V. Electrophoretic behavior of d(GGAAAAAAGG)n, d(CCAAAAAACC)n, and (CCAAAAAAGG)n and implications for a DNA bending model. Nucleic Acids Res. 1990 Feb 25;18(4):989–992. doi: 10.1093/nar/18.4.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bossi L., Smith D. M. Conformational change in the DNA associated with an unusual promoter mutation in a tRNA operon of Salmonella. Cell. 1984 Dec;39(3 Pt 2):643–652. doi: 10.1016/0092-8674(84)90471-9. [DOI] [PubMed] [Google Scholar]
  3. Brash D. E., Haseltine W. A. UV-induced mutation hotspots occur at DNA damage hotspots. Nature. 1982 Jul 8;298(5870):189–192. doi: 10.1038/298189a0. [DOI] [PubMed] [Google Scholar]
  4. Calladine C. R., Drew H. R., McCall M. J. The intrinsic curvature of DNA in solution. J Mol Biol. 1988 May 5;201(1):127–137. doi: 10.1016/0022-2836(88)90444-5. [DOI] [PubMed] [Google Scholar]
  5. Ciarrocchi G., Pedrini A. M. Determination of pyrimidine dimer unwinding angle by measurement of DNA electrophoretic mobility. J Mol Biol. 1982 Feb 25;155(2):177–183. doi: 10.1016/0022-2836(82)90445-4. [DOI] [PubMed] [Google Scholar]
  6. Cicerone R. J. Changes in stratospheric ozone. Science. 1987 Jul 3;237(4810):35–42. doi: 10.1126/science.237.4810.35. [DOI] [PubMed] [Google Scholar]
  7. Coohill T. P., Peak M. J., Peak J. G. The effects of the ultraviolet wavelengths of radiation present in sunlight on human cells in vitro. Photochem Photobiol. 1987 Dec;46(6):1043–1050. doi: 10.1111/j.1751-1097.1987.tb04891.x. [DOI] [PubMed] [Google Scholar]
  8. Crothers D. M., Haran T. E., Nadeau J. G. Intrinsically bent DNA. J Biol Chem. 1990 May 5;265(13):7093–7096. [PubMed] [Google Scholar]
  9. Dahlback A., Henriksen T., Larsen S. H., Stamnes K. Biological UV-doses and the effect of an ozone layer depletion. Photochem Photobiol. 1989 May;49(5):621–625. doi: 10.1111/j.1751-1097.1989.tb08433.x. [DOI] [PubMed] [Google Scholar]
  10. Diekmann S., von Kitzing E., McLaughlin L., Ott J., Eckstein F. The influence of exocyclic substituents of purine bases on DNA curvature. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8257–8261. doi: 10.1073/pnas.84.23.8257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hagerman P. J. Sequence-directed curvature of DNA. Nature. 1986 May 22;321(6068):449–450. doi: 10.1038/321449a0. [DOI] [PubMed] [Google Scholar]
  12. Hagerman P. J. Sequence-directed curvature of DNA. Annu Rev Biochem. 1990;59:755–781. doi: 10.1146/annurev.bi.59.070190.003543. [DOI] [PubMed] [Google Scholar]
  13. Husain I., Griffith J., Sancar A. Thymine dimers bend DNA. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2558–2562. doi: 10.1073/pnas.85.8.2558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kemmink J., Boelens R., Koning T. M., Kaptein R., van der Marel G. A., van Boom J. H. Conformational changes in the oligonucleotide duplex d(GCGTTGCG) x d(CGCAACGC) induced by formation of a cis-syn thymine dimer. A two-dimensional NMR study. Eur J Biochem. 1987 Jan 2;162(1):37–43. doi: 10.1111/j.1432-1033.1987.tb10538.x. [DOI] [PubMed] [Google Scholar]
  15. Kemmink J., Boelens R., Koning T., van der Marel G. A., van Boom J. H., Kaptein R. 1H NMR study of the exchangeable protons of the duplex d(GCGTTGCG).d(CGCAACGC) containing a thymine photodimer. Nucleic Acids Res. 1987 Jun 11;15(11):4645–4653. doi: 10.1093/nar/15.11.4645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Koo H. S., Crothers D. M. Calibration of DNA curvature and a unified description of sequence-directed bending. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1763–1767. doi: 10.1073/pnas.85.6.1763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koo H. S., Crothers D. M. Chemical determinants of DNA bending at adenine-thymine tracts. Biochemistry. 1987 Jun 16;26(12):3745–3748. doi: 10.1021/bi00386a070. [DOI] [PubMed] [Google Scholar]
  18. Koo H. S., Drak J., Rice J. A., Crothers D. M. Determination of the extent of DNA bending by an adenine-thymine tract. Biochemistry. 1990 May 1;29(17):4227–4234. doi: 10.1021/bi00469a027. [DOI] [PubMed] [Google Scholar]
  19. Koo H. S., Wu H. M., Crothers D. M. DNA bending at adenine . thymine tracts. Nature. 1986 Apr 10;320(6062):501–506. doi: 10.1038/320501a0. [DOI] [PubMed] [Google Scholar]
  20. Miller J. H. Mutagenic specificity of ultraviolet light. J Mol Biol. 1985 Mar 5;182(1):45–65. doi: 10.1016/0022-2836(85)90026-9. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Pearlman D. A., Holbrook S. R., Pirkle D. H., Kim S. H. Molecular models for DNA damaged by photoreaction. Science. 1985 Mar 15;227(4692):1304–1308. doi: 10.1126/science.3975615. [DOI] [PubMed] [Google Scholar]
  23. Rao S. N., Keepers J. W., Kollman P. The structure of d(CGCGAAT[]TCGCG) . d(CGCGAATTCGCG); the incorporation of a thymine photodimer into a B-DNA helix. Nucleic Acids Res. 1984 Jun 11;12(11):4789–4807. doi: 10.1093/nar/12.11.4789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ross W., Shulman M., Landy A. Biochemical analysis of att-defective mutants of the phage lambda site-specific recombination system. J Mol Biol. 1982 Apr 15;156(3):505–522. doi: 10.1016/0022-2836(82)90263-7. [DOI] [PubMed] [Google Scholar]
  25. Rycyna R. E., Wallace J. C., Sharma M., Alderfer J. L. Ultraviolet irradiation of nucleic acids: formation, purification, and solution conformational analyses of oligothymidylates containing cis-syn photodimers. Biochemistry. 1988 May 3;27(9):3152–3163. doi: 10.1021/bi00409a006. [DOI] [PubMed] [Google Scholar]
  26. Seela F., Berg H., Rosemeyer H. Bending of oligonucleotides containing an isosteric nucleobase: 7-deaza-2'-deoxyadenosine replacing dA within d(A)6 tracts. Biochemistry. 1989 Jul 25;28(15):6193–6198. doi: 10.1021/bi00441a010. [DOI] [PubMed] [Google Scholar]
  27. Taylor J. S., Garrett D. S., Brockie I. R., Svoboda D. L., Telser J. 1H NMR assignment and melting temperature study of cis-syn and trans-syn thymine dimer containing duplexes of d(CGTATTATGC).d(GCATAATACG). Biochemistry. 1990 Sep 18;29(37):8858–8866. doi: 10.1021/bi00489a049. [DOI] [PubMed] [Google Scholar]
  28. Wu H. M., Crothers D. M. The locus of sequence-directed and protein-induced DNA bending. Nature. 1984 Apr 5;308(5959):509–513. doi: 10.1038/308509a0. [DOI] [PubMed] [Google Scholar]
  29. Zahn K., Blattner F. R. Direct evidence for DNA bending at the lambda replication origin. Science. 1987 Apr 24;236(4800):416–422. doi: 10.1126/science.2951850. [DOI] [PubMed] [Google Scholar]

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