Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1999 Jan 15;18(2):433–443. doi: 10.1093/emboj/18.2.433

TATA-binding protein promotes the selective formation of UV-induced (6-4)-photoproducts and modulates DNA repair in the TATA box.

A Aboussekhra 1, F Thoma 1
PMCID: PMC1171137  PMID: 9889199

Abstract

DNA-damage formation and repair are coupled to the structure and accessibility of DNA in chromatin. DNA damage may compromise protein binding, thereby affecting function. We have studied the effect of TATA-binding protein (TBP) on damage formation by ultraviolet light and on DNA repair by photolyase and nucleotide excision repair in yeast and in vitro. In vivo, selective and enhanced formation of (6-4)-photoproducts (6-4PPs) was found within the TATA boxes of the active SNR6 and GAL10 genes, engaged in transcription initiation by RNA polymerase III and RNA polymerase II, respectively. Cyclobutane pyrimidine dimers (CPDs) were generated at the edge and outside of the TATA boxes, and in the inactive promoters. The same selective and enhanced 6-4PP formation was observed in a TBP-TATA complex in vitro at sites where crystal structures revealed bent DNA. We conclude that similar DNA distortions occur in vivo when TBP is part of the initiation complexes. Repair analysis by photolyase revealed inhibition of CPD repair at the edge of the TATA box in the active SNR6 promoter in vitro, but not in the GAL10 TATA box or in the inactive SNR6 promoter. Nucleotide excision repair was not inhibited, but preferentially repaired the 6-4PPs. We conclude that TBP can remain bound to damaged promoters and that nucleotide excision repair is the predominant pathway to remove UV damage in active TATA boxes.

Full Text

The Full Text of this article is available as a PDF (438.9 KB).

Selected References

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

  1. Aboussekhra A., Thoma F. Nucleotide excision repair and photolyase preferentially repair the nontranscribed strand of RNA polymerase III-transcribed genes in Saccharomyces cerevisiae. Genes Dev. 1998 Feb 1;12(3):411–421. doi: 10.1101/gad.12.3.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Auble D. T., Hahn S. An ATP-dependent inhibitor of TBP binding to DNA. Genes Dev. 1993 May;7(5):844–856. doi: 10.1101/gad.7.5.844. [DOI] [PubMed] [Google Scholar]
  3. Becker M. M., Lesser D., Kurpiewski M., Baranger A., Jen-Jacobson L. "Ultraviolet footprinting" accurately maps sequence-specific contacts and DNA kinking in the EcoRI endonuclease-DNA complex. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6247–6251. doi: 10.1073/pnas.85.17.6247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Becker M. M., Wang J. C. Use of light for footprinting DNA in vivo. Nature. 1984 Jun 21;309(5970):682–687. doi: 10.1038/309682a0. [DOI] [PubMed] [Google Scholar]
  5. Becker M. M., Wang Z., Grossmann G., Becherer K. A. Genomic footprinting in mammalian cells with ultraviolet light. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5315–5319. doi: 10.1073/pnas.86.14.5315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Becker M. M., Wang Z. Origin of ultraviolet damage in DNA. J Mol Biol. 1989 Dec 5;210(3):429–438. doi: 10.1016/0022-2836(89)90120-4. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Brow D. A., Guthrie C. Transcription of a yeast U6 snRNA gene requires a polymerase III promoter element in a novel position. Genes Dev. 1990 Aug;4(8):1345–1356. doi: 10.1101/gad.4.8.1345. [DOI] [PubMed] [Google Scholar]
  9. Brown D. W., Libertini L. J., Suquet C., Small E. W., Smerdon M. J. Unfolding of nucleosome cores dramatically changes the distribution of ultraviolet photoproducts in DNA. Biochemistry. 1993 Oct 12;32(40):10527–10531. doi: 10.1021/bi00091a001. [DOI] [PubMed] [Google Scholar]
  10. Burley S. K., Roeder R. G. Biochemistry and structural biology of transcription factor IID (TFIID). Annu Rev Biochem. 1996;65:769–799. doi: 10.1146/annurev.bi.65.070196.004005. [DOI] [PubMed] [Google Scholar]
  11. Burnol A. F., Margottin F., Huet J., Almouzni G., Prioleau M. N., Méchali M., Sentenac A. TFIIIC relieves repression of U6 snRNA transcription by chromatin. Nature. 1993 Apr 1;362(6419):475–477. doi: 10.1038/362475a0. [DOI] [PubMed] [Google Scholar]
  12. Christians F. C., Hanawalt P. C. Lack of transcription-coupled repair in mammalian ribosomal RNA genes. Biochemistry. 1993 Oct 5;32(39):10512–10518. doi: 10.1021/bi00090a030. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Colbert T., Lee S., Schimmack G., Hahn S. Architecture of protein and DNA contacts within the TFIIIB-DNA complex. Mol Cell Biol. 1998 Mar;18(3):1682–1691. doi: 10.1128/mcb.18.3.1682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dammann R., Pfeifer G. P. Lack of gene- and strand-specific DNA repair in RNA polymerase III-transcribed human tRNA genes. Mol Cell Biol. 1997 Jan;17(1):219–229. doi: 10.1128/mcb.17.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Donahue B. A., Yin S., Taylor J. S., Reines D., Hanawalt P. C. Transcript cleavage by RNA polymerase II arrested by a cyclobutane pyrimidine dimer in the DNA template. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8502–8506. doi: 10.1073/pnas.91.18.8502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Friedberg E. C. Relationships between DNA repair and transcription. Annu Rev Biochem. 1996;65:15–42. doi: 10.1146/annurev.bi.65.070196.000311. [DOI] [PubMed] [Google Scholar]
  18. Fritz L. K., Smerdon M. J. Repair of UV damage in actively transcribed ribosomal genes. Biochemistry. 1995 Oct 10;34(40):13117–13124. doi: 10.1021/bi00040a024. [DOI] [PubMed] [Google Scholar]
  19. Gale J. M., Nissen K. A., Smerdon M. J. UV-induced formation of pyrimidine dimers in nucleosome core DNA is strongly modulated with a period of 10.3 bases. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6644–6648. doi: 10.1073/pnas.84.19.6644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gale J. M., Smerdon M. J. UV induced (6-4) photoproducts are distributed differently than cyclobutane dimers in nucleosomes. Photochem Photobiol. 1990 Apr;51(4):411–417. doi: 10.1111/j.1751-1097.1990.tb01732.x. [DOI] [PubMed] [Google Scholar]
  21. Galloway A. M., Liuzzi M., Paterson M. C. Metabolic processing of cyclobutyl pyrimidine dimers and (6-4) photoproducts in UV-treated human cells. Evidence for distinct excision-repair pathways. J Biol Chem. 1994 Jan 14;269(2):974–980. [PubMed] [Google Scholar]
  22. Gao S., Drouin R., Holmquist G. P. DNA repair rates mapped along the human PGK1 gene at nucleotide resolution. Science. 1994 Mar 11;263(5152):1438–1440. doi: 10.1126/science.8128226. [DOI] [PubMed] [Google Scholar]
  23. Geiduschek E. P., Kassavetis G. A. Comparing transcriptional initiation by RNA polymerases I and III. Curr Opin Cell Biol. 1995 Jun;7(3):344–351. doi: 10.1016/0955-0674(95)80089-1. [DOI] [PubMed] [Google Scholar]
  24. Geiger J. H., Hahn S., Lee S., Sigler P. B. Crystal structure of the yeast TFIIA/TBP/DNA complex. Science. 1996 May 10;272(5263):830–836. doi: 10.1126/science.272.5263.830. [DOI] [PubMed] [Google Scholar]
  25. Gerlach V. L., Whitehall S. K., Geiduschek E. P., Brow D. A. TFIIIB placement on a yeast U6 RNA gene in vivo is directed primarily by TFIIIC rather than by sequence-specific DNA contacts. Mol Cell Biol. 1995 Mar;15(3):1455–1466. doi: 10.1128/mcb.15.3.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Guzder S. N., Sung P., Prakash L., Prakash S. Yeast DNA-repair gene RAD14 encodes a zinc metalloprotein with affinity for ultraviolet-damaged DNA. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5433–5437. doi: 10.1073/pnas.90.12.5433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hernandez N. TBP, a universal eukaryotic transcription factor? Genes Dev. 1993 Jul;7(7B):1291–1308. doi: 10.1101/gad.7.7b.1291. [DOI] [PubMed] [Google Scholar]
  28. Kassavetis G. A., Joazeiro C. A., Pisano M., Geiduschek E. P., Colbert T., Hahn S., Blanco J. A. The role of the TATA-binding protein in the assembly and function of the multisubunit yeast RNA polymerase III transcription factor, TFIIIB. Cell. 1992 Dec 11;71(6):1055–1064. doi: 10.1016/0092-8674(92)90399-w. [DOI] [PubMed] [Google Scholar]
  29. Kim J. K., Choi B. S. The solution structure of DNA duplex-decamer containing the (6-4) photoproduct of thymidylyl(3'-->5')thymidine by NMR and relaxation matrix refinement. Eur J Biochem. 1995 Mar 15;228(3):849–854. doi: 10.1111/j.1432-1033.1995.tb20331.x. [DOI] [PubMed] [Google Scholar]
  30. Kim J. L., Nikolov D. B., Burley S. K. Co-crystal structure of TBP recognizing the minor groove of a TATA element. Nature. 1993 Oct 7;365(6446):520–527. doi: 10.1038/365520a0. [DOI] [PubMed] [Google Scholar]
  31. Kim Y., Geiger J. H., Hahn S., Sigler P. B. Crystal structure of a yeast TBP/TATA-box complex. Nature. 1993 Oct 7;365(6446):512–520. doi: 10.1038/365512a0. [DOI] [PubMed] [Google Scholar]
  32. Lindahl T. Instability and decay of the primary structure of DNA. Nature. 1993 Apr 22;362(6422):709–715. doi: 10.1038/362709a0. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Liu X., Conconi A., Smerdon M. J. Strand-specific modulation of UV photoproducts in 5S rDNA by TFIIIA binding and their effect on TFIIIA complex formation. Biochemistry. 1997 Nov 4;36(44):13710–13717. doi: 10.1021/bi9716736. [DOI] [PubMed] [Google Scholar]
  35. Livingstone-Zatchej M., Meier A., Suter B., Thoma F. RNA polymerase II transcription inhibits DNA repair by photolyase in the transcribed strand of active yeast genes. Nucleic Acids Res. 1997 Oct 1;25(19):3795–3800. doi: 10.1093/nar/25.19.3795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lyamichev V. I., Frank-Kamenetskii M. D., Soyfer V. N. Protection against UV-induced pyrimidine dimerization in DNA by triplex formation. Nature. 1990 Apr 5;344(6266):568–570. doi: 10.1038/344568a0. [DOI] [PubMed] [Google Scholar]
  37. Lyamichev V. Unusual conformation of (dA)n.(dT)n-tracts as revealed by cyclobutane thymine-thymine dimer formation. Nucleic Acids Res. 1991 Aug 25;19(16):4491–4496. doi: 10.1093/nar/19.16.4491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mann D. B., Springer D. L., Smerdon M. J. DNA damage can alter the stability of nucleosomes: effects are dependent on damage type. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2215–2220. doi: 10.1073/pnas.94.6.2215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Marsolier M. C., Tanaka S., Livingstone-Zatchej M., Grunstein M., Thoma F., Sentenac A. Reciprocal interferences between nucleosomal organization and transcriptional activity of the yeast SNR6 gene. Genes Dev. 1995 Feb 15;9(4):410–422. doi: 10.1101/gad.9.4.410. [DOI] [PubMed] [Google Scholar]
  40. McCready S., Cox B. Repair of 6-4 photoproducts in Saccharomyces cerevisiae. Mutat Res. 1993 Mar;293(3):233–240. doi: 10.1016/0921-8777(93)90074-q. [DOI] [PubMed] [Google Scholar]
  41. Nikolov D. B., Chen H., Halay E. D., Usheva A. A., Hisatake K., Lee D. K., Roeder R. G., Burley S. K. Crystal structure of a TFIIB-TBP-TATA-element ternary complex. Nature. 1995 Sep 14;377(6545):119–128. doi: 10.1038/377119a0. [DOI] [PubMed] [Google Scholar]
  42. Orphanides G., Lagrange T., Reinberg D. The general transcription factors of RNA polymerase II. Genes Dev. 1996 Nov 1;10(21):2657–2683. doi: 10.1101/gad.10.21.2657. [DOI] [PubMed] [Google Scholar]
  43. Patikoglou G., Burley S. K. Eukaryotic transcription factor-DNA complexes. Annu Rev Biophys Biomol Struct. 1997;26:289–325. doi: 10.1146/annurev.biophys.26.1.289. [DOI] [PubMed] [Google Scholar]
  44. Pehrson J. R., Cohen L. H. Effects of DNA looping on pyrimidine dimer formation. Nucleic Acids Res. 1992 Mar 25;20(6):1321–1324. doi: 10.1093/nar/20.6.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Pehrson J. R. Thymine dimer formation as a probe of the path of DNA in and between nucleosomes in intact chromatin. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9149–9153. doi: 10.1073/pnas.86.23.9149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Pfeifer G. P., Drouin R., Riggs A. D., Holmquist G. P. Binding of transcription factors creates hot spots for UV photoproducts in vivo. Mol Cell Biol. 1992 Apr;12(4):1798–1804. doi: 10.1128/mcb.12.4.1798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sage E. Distribution and repair of photolesions in DNA: genetic consequences and the role of sequence context. Photochem Photobiol. 1993 Jan;57(1):163–174. doi: 10.1111/j.1751-1097.1993.tb02273.x. [DOI] [PubMed] [Google Scholar]
  48. Sancar A. DNA excision repair. Annu Rev Biochem. 1996;65:43–81. doi: 10.1146/annurev.bi.65.070196.000355. [DOI] [PubMed] [Google Scholar]
  49. Sancar A. No "End of History" for photolyases. Science. 1996 Apr 5;272(5258):48–49. doi: 10.1126/science.272.5258.48. [DOI] [PubMed] [Google Scholar]
  50. Schieferstein U., Thoma F. Modulation of cyclobutane pyrimidine dimer formation in a positioned nucleosome containing poly(dA.dT) tracts. Biochemistry. 1996 Jun 18;35(24):7705–7714. doi: 10.1021/bi953011r. [DOI] [PubMed] [Google Scholar]
  51. Schieferstein U., Thoma F. Site-specific repair of cyclobutane pyrimidine dimers in a positioned nucleosome by photolyase and T4 endonuclease V in vitro. EMBO J. 1998 Jan 2;17(1):306–316. doi: 10.1093/emboj/17.1.306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Selby C. P., Sancar A. Mechanisms of transcription-repair coupling and mutation frequency decline. Microbiol Rev. 1994 Sep;58(3):317–329. doi: 10.1128/mr.58.3.317-329.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Selleck S. B., Majors J. E. In vivo DNA-binding properties of a yeast transcription activator protein. Mol Cell Biol. 1987 Sep;7(9):3260–3267. doi: 10.1128/mcb.7.9.3260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Selleck S. B., Majors J. In vivo "photofootprint" changes at sequences between the yeast GAL1 upstream activating sequence and "TATA" element require activated GAL4 protein but not a functional TATA element. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5399–5403. doi: 10.1073/pnas.85.15.5399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Selleck S. B., Majors J. Photofootprinting in vivo detects transcription-dependent changes in yeast TATA boxes. Nature. 1987 Jan 8;325(7000):173–177. doi: 10.1038/325173a0. [DOI] [PubMed] [Google Scholar]
  56. Suquet C., Mitchell D. L., Smerdon M. J. Repair of UV-induced (6-4) photoproducts in nucleosome core DNA. J Biol Chem. 1995 Jul 14;270(28):16507–16509. doi: 10.1074/jbc.270.28.16507. [DOI] [PubMed] [Google Scholar]
  57. Suquet C., Smerdon M. J. UV damage to DNA strongly influences its rotational setting on the histone surface of reconstituted nucleosomes. J Biol Chem. 1993 Nov 15;268(32):23755–23757. [PubMed] [Google Scholar]
  58. Suter B., Livingstone-Zatchej M., Thoma F. Chromatin structure modulates DNA repair by photolyase in vivo. EMBO J. 1997 Apr 15;16(8):2150–2160. doi: 10.1093/emboj/16.8.2150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Szymkowski D. E., Lawrence C. W., Wood R. D. Repair by human cell extracts of single (6-4) and cyclobutane thymine-thymine photoproducts in DNA. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9823–9827. doi: 10.1073/pnas.90.21.9823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Tan S., Hunziker Y., Sargent D. F., Richmond T. J. Crystal structure of a yeast TFIIA/TBP/DNA complex. Nature. 1996 May 9;381(6578):127–151. doi: 10.1038/381127a0. [DOI] [PubMed] [Google Scholar]
  61. Teng Y., Li S., Waters R., Reed S. H. Excision repair at the level of the nucleotide in the Saccharomyces cerevisiae MFA2 gene: mapping of where enhanced repair in the transcribed strand begins or ends and identification of only a partial rad16 requisite for repairing upstream control sequences. J Mol Biol. 1997 Mar 28;267(2):324–337. doi: 10.1006/jmbi.1996.0908. [DOI] [PubMed] [Google Scholar]
  62. Tommasi S., Swiderski P. M., Tu Y., Kaplan B. E., Pfeifer G. P. Inhibition of transcription factor binding by ultraviolet-induced pyrimidine dimers. Biochemistry. 1996 Dec 10;35(49):15693–15703. doi: 10.1021/bi962117z. [DOI] [PubMed] [Google Scholar]
  63. Tornaletti S., Pfeifer G. P. UV damage and repair mechanisms in mammalian cells. Bioessays. 1996 Mar;18(3):221–228. doi: 10.1002/bies.950180309. [DOI] [PubMed] [Google Scholar]
  64. Tornaletti S., Pfeifer G. P. UV light as a footprinting agent: modulation of UV-induced DNA damage by transcription factors bound at the promoters of three human genes. J Mol Biol. 1995 Jun 16;249(4):714–728. doi: 10.1006/jmbi.1995.0331. [DOI] [PubMed] [Google Scholar]
  65. Tu Y., Tornaletti S., Pfeifer G. P. DNA repair domains within a human gene: selective repair of sequences near the transcription initiation site. EMBO J. 1996 Feb 1;15(3):675–683. [PMC free article] [PubMed] [Google Scholar]
  66. Vichi P., Coin F., Renaud J. P., Vermeulen W., Hoeijmakers J. H., Moras D., Egly J. M. Cisplatin- and UV-damaged DNA lure the basal transcription factor TFIID/TBP. EMBO J. 1997 Dec 15;16(24):7444–7456. doi: 10.1093/emboj/16.24.7444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Wang C. I., Taylor J. S. Site-specific effect of thymine dimer formation on dAn.dTn tract bending and its biological implications. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9072–9076. doi: 10.1073/pnas.88.20.9072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wellinger R. E., Thoma F. Nucleosome structure and positioning modulate nucleotide excision repair in the non-transcribed strand of an active gene. EMBO J. 1997 Aug 15;16(16):5046–5056. doi: 10.1093/emboj/16.16.5046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Wellinger R. E., Thoma F. Taq DNA polymerase blockage at pyrimidine dimers. Nucleic Acids Res. 1996 Apr 15;24(8):1578–1579. doi: 10.1093/nar/24.8.1578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Wood R. D. DNA repair in eukaryotes. Annu Rev Biochem. 1996;65:135–167. doi: 10.1146/annurev.bi.65.070196.001031. [DOI] [PubMed] [Google Scholar]
  71. Yajima H., Takao M., Yasuhira S., Zhao J. H., Ishii C., Inoue H., Yasui A. A eukaryotic gene encoding an endonuclease that specifically repairs DNA damaged by ultraviolet light. EMBO J. 1995 May 15;14(10):2393–2399. doi: 10.1002/j.1460-2075.1995.tb07234.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Yasui A., Eker A. P., Yasuhira S., Yajima H., Kobayashi T., Takao M., Oikawa A. A new class of DNA photolyases present in various organisms including aplacental mammals. EMBO J. 1994 Dec 15;13(24):6143–6151. doi: 10.1002/j.1460-2075.1994.tb06961.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES