Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1985 Jul 25;13(14):5317–5325. doi: 10.1093/nar/13.14.5317

Structural determination of the ultraviolet light-induced thymine-cytosine pyrimidine-pyrimidone (6-4) photoproduct.

W A Franklin, P W Doetsch, W A Haseltine
PMCID: PMC321867  PMID: 4022781

Abstract

Ultraviolet light induces damage to DNA, with the majority of the damage expressed as the formation of cyclobutane dimers and pyrimidine-pyrimidone (6-4) photoproducts. The (6-4) photoproducts have been implicated as important UV light-induced premutagenic DNA lesions. The most abundant of the (6-4) products is the thymine-cytosine pyrimidine-pyrimidone (6-4) photoproduct, or TC (6-4) product. The structure of the TC (6-4) product was deduced by proton NMR, IR, and fast atom bombardment mass spectroscopy, and the product was found to differ from the previously described photoadduct, Thy(6-4)Pyo, by the presence of an amino group at the 5 position of the 5' pyrimidine. The implications of this structure on DNA base pairing and the induction of ultraviolet light-induced mutations are discussed.

Full text

PDF
5317

Selected References

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

  1. 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]
  2. Davies D. B., Danyluk S. S. Nuclear magnetic resonance studies of 5'-ribo- and deoxyribonucleotide structures in solution. Biochemistry. 1974 Oct 8;13(21):4417–4434. doi: 10.1021/bi00718a027. [DOI] [PubMed] [Google Scholar]
  3. Franklin W. A., Haseltine W. A. Removal of UV light-induced pyrimidine-pyrimidone(6-4) products from Escherichia coli DNA requires the uvrA, uvrB, and urvC gene products. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3821–3824. doi: 10.1073/pnas.81.12.3821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Franklin W. A., Lo K. M., Haseltine W. A. Alkaline lability of fluorescent photoproducts produced in ultraviolet light-irradiated DNA. J Biol Chem. 1982 Nov 25;257(22):13535–13543. [PubMed] [Google Scholar]
  5. Hanawalt P. C., Cooper P. K., Ganesan A. K., Smith C. A. DNA repair in bacteria and mammalian cells. Annu Rev Biochem. 1979;48:783–836. doi: 10.1146/annurev.bi.48.070179.004031. [DOI] [PubMed] [Google Scholar]
  6. Haseltine W. A. Ultraviolet light repair and mutagenesis revisited. Cell. 1983 May;33(1):13–17. doi: 10.1016/0092-8674(83)90329-x. [DOI] [PubMed] [Google Scholar]
  7. Karle I. L. Crystal structure of a thymine-thymine adduct from irradiated thymine. Acta Crystallogr B. 1969 Oct 15;25(10):2119–2126. doi: 10.1107/s056774086900522x. [DOI] [PubMed] [Google Scholar]
  8. Karle I. L., Wang S. Y., Varghese A. J. Crystal and molecular structure of a thymine-thymine adduct. Science. 1969 Apr 11;164(3876):183–184. doi: 10.1126/science.164.3876.183. [DOI] [PubMed] [Google Scholar]
  9. Langhammer R., Piechocki R. Comparative analysis of UV-induced mutability of ten different codon units in position 211 of the Escherichia coli trpA gene. Mol Gen Genet. 1984;196(3):530–532. doi: 10.1007/BF00436204. [DOI] [PubMed] [Google Scholar]
  10. Lippke J. A., Gordon L. K., Brash D. E., Haseltine W. A. Distribution of UV light-induced damage in a defined sequence of human DNA: detection of alkaline-sensitive lesions at pyrimidine nucleoside-cytidine sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3388–3392. doi: 10.1073/pnas.78.6.3388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Liu F. T., Yang N. C. Photochemistry of cytosine derivatives. 1. Photochemistry of thymidylyl-(3' leads to 5')-deoxycytidine. Biochemistry. 1978 Nov 14;17(23):4865–4876. doi: 10.1021/bi00616a003. [DOI] [PubMed] [Google Scholar]
  12. Miller J. H. Mutational specificity in bacteria. Annu Rev Genet. 1983;17:215–238. doi: 10.1146/annurev.ge.17.120183.001243. [DOI] [PubMed] [Google Scholar]
  13. Rhoades D. F., Wang S. Y. Uracil-thymine adduct from a mixture of uracil and thymine irradiated with ultraviolet light. Biochemistry. 1970 Oct 27;9(22):4416–4420. doi: 10.1021/bi00824a024. [DOI] [PubMed] [Google Scholar]
  14. Sagher D., Strauss B. Insertion of nucleotides opposite apurinic/apyrimidinic sites in deoxyribonucleic acid during in vitro synthesis: uniqueness of adenine nucleotides. Biochemistry. 1983 Sep 13;22(19):4518–4526. doi: 10.1021/bi00288a026. [DOI] [PubMed] [Google Scholar]
  15. Sancar A., Rupp W. D. A novel repair enzyme: UVRABC excision nuclease of Escherichia coli cuts a DNA strand on both sides of the damaged region. Cell. 1983 May;33(1):249–260. doi: 10.1016/0092-8674(83)90354-9. [DOI] [PubMed] [Google Scholar]
  16. Varghese A. J., Patrick M. H. Cytosine derived heteroadduct formation in ultraviolet-irradiated DNA. Nature. 1969 Jul 19;223(5203):299–300. doi: 10.1038/223299a0. [DOI] [PubMed] [Google Scholar]
  17. Varghese A. J. Photochemistry of nucleic acids and their constituents. Photophysiology. 1972;(7):207–274. [PubMed] [Google Scholar]
  18. Varghese A. J., Wang S. Y. Thymine-thymine adduct as a photoproduct of thymine. Science. 1968 Apr 12;160(3824):186–187. doi: 10.1126/science.160.3824.186. [DOI] [PubMed] [Google Scholar]
  19. Varghese A. J., Wang S. Y. Ultraviolet irradiation of DNA in vitro and in vivo produces a 3d thymine-derived product. Science. 1967 May 19;156(3777):955–957. doi: 10.1126/science.156.3777.955. [DOI] [PubMed] [Google Scholar]
  20. Wang S. Y., Varghese A. J. Cytosine-thymine addition product from DNA irradiated with ultraviolet light. Biochem Biophys Res Commun. 1967 Nov 30;29(4):543–549. doi: 10.1016/0006-291x(67)90519-0. [DOI] [PubMed] [Google Scholar]
  21. Witkin E. M. Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli. Bacteriol Rev. 1976 Dec;40(4):869–907. doi: 10.1128/br.40.4.869-907.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wood R. D., Skopek T. R., Hutchinson F. Changes in DNA base sequence induced by targeted mutagenesis of lambda phage by ultraviolet light. J Mol Biol. 1984 Mar 5;173(3):273–291. doi: 10.1016/0022-2836(84)90121-9. [DOI] [PubMed] [Google Scholar]

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

RESOURCES