Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1998 Jul 15;26(14):3397–3403. doi: 10.1093/nar/26.14.3397

Rapid changes of nucleotide excision repair gene expression following UV-irradiation and cisplatin treatment of Dictyostelium discoideum.

S L Yu 1, S K Lee 1, H Alexander 1, S Alexander 1
PMCID: PMC147717  PMID: 9649625

Abstract

Organisms use different mechanisms to detect and repair different types of DNA damage, and different species vary in their sensitivity to DNA damaging agents. The cellular slime mold Dictyostelium discoideum has long been recognized for its unusual resistance to UV and ionizing radiation. We have recently cloned three nucleotide excision repair (NER) genes from Dictyostelium , the rep B, D and E genes (the homologs of the human xeroderma pigmentosum group B, D and E genes, respectively). Each of these genes has a unique pattern of expression during the multicellular development of this organism. We have now examined the response of these genes to DNA damage. The rep B and D DNA helicase genes are rapidly and transiently induced in a dose dependent manner following exposure to both UV-light and the widely used chemotherapeutic agent cisplatin. Interestingly, the rep E mRNA level is repressed by UV but not by cisplatin, implying unique signal transduction pathways for recognizing and repairing different types of damage. Cells from all stages of growth and development display the same pattern of NER gene expression following exposure to UV-light. These results suggest that the response to UV is independent of DNA replication, and that all the factors necessary for rapid transcription of these NER genes are either stable throughout development, or are continuously synthesized. It is significant that the up-regulation of the rep B and D genes in response to UV and chemical damage has not been observed to occur in cells from other species. We suggest that this rapid expression of NER genes is at least in part responsible for the unusual resistance of Dictyostelium to DNA damage.

Full Text

The Full Text of this article is available as a PDF (312.0 KB).

Selected References

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

  1. Alexander H., Lee S. K., Yu S. L., Alexander S. repE--the Dictyostelium homolog of the human xeroderma pigmentosum group E gene is developmentally regulated and contains a leucine zipper motif. Nucleic Acids Res. 1996 Jun 15;24(12):2295–2301. doi: 10.1093/nar/24.12.2295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alexander S., Leone S., Ostermeyer E. Translational control of discoidin lectin expression in drsA suppressor mutants of Dictyostelium discoideum. Mol Cell Biol. 1991 Jun;11(6):3171–3179. doi: 10.1128/mcb.11.6.3171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bellon S. F., Coleman J. H., Lippard S. J. DNA unwinding produced by site-specific intrastrand cross-links of the antitumor drug cis-diamminedichloroplatinum(II). Biochemistry. 1991 Aug 13;30(32):8026–8035. doi: 10.1021/bi00246a021. [DOI] [PubMed] [Google Scholar]
  4. Bootsma D., Hoeijmakers J. H. The molecular basis of nucleotide excision repair syndromes. Mutat Res. 1994 May 1;307(1):15–23. doi: 10.1016/0027-5107(94)90273-9. [DOI] [PubMed] [Google Scholar]
  5. Bronner C. E., Welker D. L., Deering R. A. Mutations affecting sensitivity of the cellular slime mold Dictyostelium discoideum to DNA-damaging agents. Mutat Res. 1992 Sep;274(3):187–200. doi: 10.1016/0921-8777(92)90065-b. [DOI] [PubMed] [Google Scholar]
  6. Chu G. Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair. J Biol Chem. 1994 Jan 14;269(2):787–790. [PubMed] [Google Scholar]
  7. Chu G., Chang E. Cisplatin-resistant cells express increased levels of a factor that recognizes damaged DNA. Proc Natl Acad Sci U S A. 1990 May;87(9):3324–3327. doi: 10.1073/pnas.87.9.3324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chu G., Chang E. Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA. Science. 1988 Oct 28;242(4878):564–567. doi: 10.1126/science.3175673. [DOI] [PubMed] [Google Scholar]
  9. Chu G., Mayne L. Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy: do the genes explain the diseases? Trends Genet. 1996 May;12(5):187–192. doi: 10.1016/0168-9525(96)10021-4. [DOI] [PubMed] [Google Scholar]
  10. Cocucci S. M., Sussman M. RNA in cytoplasmic and nuclear fractions of cellular slime mold amebas. J Cell Biol. 1970 May;45(2):399–407. doi: 10.1083/jcb.45.2.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Deering R. A. DNA repair in Dictyostelium. Dev Genet. 1988;9(4-5):483–493. doi: 10.1002/dvg.1020090425. [DOI] [PubMed] [Google Scholar]
  12. Devary Y., Rosette C., DiDonato J. A., Karin M. NF-kappa B activation by ultraviolet light not dependent on a nuclear signal. Science. 1993 Sep 10;261(5127):1442–1445. doi: 10.1126/science.8367725. [DOI] [PubMed] [Google Scholar]
  13. Drapkin R., Reardon J. T., Ansari A., Huang J. C., Zawel L., Ahn K., Sancar A., Reinberg D. Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II. Nature. 1994 Apr 21;368(6473):769–772. doi: 10.1038/368769a0. [DOI] [PubMed] [Google Scholar]
  14. Eller M. S., Maeda T., Magnoni C., Atwal D., Gilchrest B. A. Enhancement of DNA repair in human skin cells by thymidine dinucleotides: evidence for a p53-mediated mammalian SOS response. Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12627–12632. doi: 10.1073/pnas.94.23.12627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Engelberg D., Klein C., Martinetto H., Struhl K., Karin M. The UV response involving the Ras signaling pathway and AP-1 transcription factors is conserved between yeast and mammals. Cell. 1994 May 6;77(3):381–390. doi: 10.1016/0092-8674(94)90153-8. [DOI] [PubMed] [Google Scholar]
  16. Feldberg R. S., Grossman L. A DNA binding protein from human placenta specific for ultraviolet damaged DNA. Biochemistry. 1976 Jun 1;15(11):2402–2408. doi: 10.1021/bi00656a024. [DOI] [PubMed] [Google Scholar]
  17. Fichtinger-Schepman A. M., van der Veer J. L., den Hartog J. H., Lohman P. H., Reedijk J. Adducts of the antitumor drug cis-diamminedichloroplatinum(II) with DNA: formation, identification, and quantitation. Biochemistry. 1985 Jan 29;24(3):707–713. doi: 10.1021/bi00324a025. [DOI] [PubMed] [Google Scholar]
  18. Fox M. E., Feldman B. J., Chu G. A novel role for DNA photolyase: binding to DNA damaged by drugs is associated with enhanced cytotoxicity in Saccharomyces cerevisiae. Mol Cell Biol. 1994 Dec;14(12):8071–8077. doi: 10.1128/mcb.14.12.8071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Franke J., Kessin R. A defined minimal medium for axenic strains of Dictyostelium discoideum. Proc Natl Acad Sci U S A. 1977 May;74(5):2157–2161. doi: 10.1073/pnas.74.5.2157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Freeland T. M., Guyer R. B., Ling A. Z., Deering R. A. Apurinic/apyrimidinic (AP) endonuclease from Dictyostelium discoideum: cloning, nucleotide sequence and induction by sublethal levels of DNA damaging agents. Nucleic Acids Res. 1996 May 15;24(10):1950–1953. doi: 10.1093/nar/24.10.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Hanawalt P., Mellon I. Stranded in an active gene. Curr Biol. 1993 Jan;3(1):67–69. doi: 10.1016/0960-9822(93)90156-i. [DOI] [PubMed] [Google Scholar]
  23. Hansson J., Edgren M. R., Egyházi S., Hao X. Y., Mannervik B., Ringborg U. Increased cisplatin sensitivity of human fibroblasts from a subject with inherent glutathione deficiency. Acta Oncol. 1996;35(6):683–690. doi: 10.3109/02841869609083999. [DOI] [PubMed] [Google Scholar]
  24. Hayes S., Shiyanov P., Chen X., Raychaudhuri P. DDB, a putative DNA repair protein, can function as a transcriptional partner of E2F1. Mol Cell Biol. 1998 Jan;18(1):240–249. doi: 10.1128/mcb.18.1.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hirschfeld S., Levine A. S., Ozato K., Protić M. A constitutive damage-specific DNA-binding protein is synthesized at higher levels in UV-irradiated primate cells. Mol Cell Biol. 1990 May;10(5):2041–2048. doi: 10.1128/mcb.10.5.2041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hughes E. N., Engelsberg B. N., Billings P. C. Purification of nuclear proteins that bind to cisplatin-damaged DNA. Identity with high mobility group proteins 1 and 2. J Biol Chem. 1992 Jul 5;267(19):13520–13527. [PubMed] [Google Scholar]
  27. Keeney S., Eker A. P., Brody T., Vermeulen W., Bootsma D., Hoeijmakers J. H., Linn S. Correction of the DNA repair defect in xeroderma pigmentosum group E by injection of a DNA damage-binding protein. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4053–4056. doi: 10.1073/pnas.91.9.4053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Khosla M., Robbins S. M., Spiegelman G. B., Weeks G. Regulation of DdrasG gene expression during Dictyostelium development. Mol Cell Biol. 1990 Mar;10(3):918–922. doi: 10.1128/mcb.10.3.918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kraemer K. H., Levy D. D., Parris C. N., Gozukara E. M., Moriwaki S., Adelberg S., Seidman M. M. Xeroderma pigmentosum and related disorders: examining the linkage between defective DNA repair and cancer. J Invest Dermatol. 1994 Nov;103(5 Suppl):96S–101S. doi: 10.1111/1523-1747.ep12399329. [DOI] [PubMed] [Google Scholar]
  30. Krishnamoorthy R. R., Lee T. H., Butel J. S., Das H. K. Apolipoprotein B gene regulatory factor-2 (BRF-2) is structurally and immunologically highly related to hepatitis B virus X associated protein-1 (XAP-1). Biochemistry. 1997 Jan 28;36(4):960–969. doi: 10.1021/bi961407c. [DOI] [PubMed] [Google Scholar]
  31. Lee S. K., Yu S. L., Alexander H., Alexander S. Increasing the specificity of colony hybridization when using heterologous probes. Biotechniques. 1996 Oct;21(4):630–632. doi: 10.2144/96214bm14. [DOI] [PubMed] [Google Scholar]
  32. Lee S. K., Yu S. L., Garcia M. X., Alexander H., Alexander S. Differential developmental expression of the rep B and rep D xeroderma pigmentosum related DNA helicase genes from Dictyostelium discoideum. Nucleic Acids Res. 1997 Jun 15;25(12):2365–2374. doi: 10.1093/nar/25.12.2365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lee T. H., Elledge S. J., Butel J. S. Hepatitis B virus X protein interacts with a probable cellular DNA repair protein. J Virol. 1995 Feb;69(2):1107–1114. doi: 10.1128/jvi.69.2.1107-1114.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Loehrer P. J., Einhorn L. H. Drugs five years later. Cisplatin. Ann Intern Med. 1984 May;100(5):704–713. doi: 10.7326/0003-4819-100-5-704. [DOI] [PubMed] [Google Scholar]
  35. Loomis W. F. Genetic tools for Dictyostelium discoideum. Methods Cell Biol. 1987;28:31–65. doi: 10.1016/s0091-679x(08)61636-2. [DOI] [PubMed] [Google Scholar]
  36. MOROWITZ H. J. Absorption effects in volume irradiation of microorganisms. Science. 1950 Mar 3;111(2879):229–229. doi: 10.1126/science.111.2879.229-a. [DOI] [PubMed] [Google Scholar]
  37. Ma L., Hoeijmakers J. H., van der Eb A. J. Mammalian nucleotide excision repair. Biochim Biophys Acta. 1995 Dec 18;1242(2):137–163. doi: 10.1016/0304-419x(95)00008-4. [DOI] [PubMed] [Google Scholar]
  38. Madura K., Prakash S. Nucleotide sequence, transcript mapping, and regulation of the RAD2 gene of Saccharomyces cerevisiae. J Bacteriol. 1986 Jun;166(3):914–923. doi: 10.1128/jb.166.3.914-923.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Madura K., Prakash S. The Saccharomyces cerevisiae DNA repair gene RAD2 is regulated in meiosis but not during the mitotic cell cycle. Mol Cell Biol. 1990 Jun;10(6):3256–3257. doi: 10.1128/mcb.10.6.3256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Mauldin S. K., Freeland T. M., Deering R. A. Differential repair of UV damage in a developmentally regulated gene of Dictyostelium discoideum. Mutat Res. 1994 Mar;314(2):187–198. doi: 10.1016/0921-8777(94)90082-5. [DOI] [PubMed] [Google Scholar]
  41. Mount D. W. DNA repair. Reprogramming transcription. Nature. 1996 Oct 31;383(6603):763–764. doi: 10.1038/383763a0. [DOI] [PubMed] [Google Scholar]
  42. Pawson T., Amiel T., Hinze E., Auersperg N., Neave N., Sobolewski A., Weeks G. Regulation of a ras-related protein during development of Dictyostelium discoideum. Mol Cell Biol. 1985 Jan;5(1):33–39. doi: 10.1128/mcb.5.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Payne A., Chu G. Xeroderma pigmentosum group E binding factor recognizes a broad spectrum of DNA damage. Mutat Res. 1994 Oct 1;310(1):89–102. doi: 10.1016/0027-5107(94)90012-4. [DOI] [PubMed] [Google Scholar]
  44. Protić M. Eukaryotic damaged DNA-binding proteins. DNA repair proteins or transcription factors? Ann N Y Acad Sci. 1994 Jul 29;726:333–335. doi: 10.1111/j.1749-6632.1994.tb52843.x. [DOI] [PubMed] [Google Scholar]
  45. Sancar A. DNA repair in humans. Annu Rev Genet. 1995;29:69–105. doi: 10.1146/annurev.ge.29.120195.000441. [DOI] [PubMed] [Google Scholar]
  46. Sancar A. Mechanisms of DNA excision repair. Science. 1994 Dec 23;266(5193):1954–1956. doi: 10.1126/science.7801120. [DOI] [PubMed] [Google Scholar]
  47. Soll D. R. Methods for manipulating and investigating developmental timing in Dictyostelium discoideum. Methods Cell Biol. 1987;28:413–431. doi: 10.1016/s0091-679x(08)61660-x. [DOI] [PubMed] [Google Scholar]
  48. Sussman M. Cultivation and synchronous morphogenesis of Dictyostelium under controlled experimental conditions. Methods Cell Biol. 1987;28:9–29. doi: 10.1016/s0091-679x(08)61635-0. [DOI] [PubMed] [Google Scholar]
  49. Svejstrup J. Q., Wang Z., Feaver W. J., Wu X., Bushnell D. A., Donahue T. F., Friedberg E. C., Kornberg R. D. Different forms of TFIIH for transcription and DNA repair: holo-TFIIH and a nucleotide excision repairosome. Cell. 1995 Jan 13;80(1):21–28. doi: 10.1016/0092-8674(95)90447-6. [DOI] [PubMed] [Google Scholar]
  50. Sweder K. S., Hanawalt P. C. The COOH terminus of suppressor of stem loop (SSL2/RAD25) in yeast is essential for overall genomic excision repair and transcription-coupled repair. J Biol Chem. 1994 Jan 21;269(3):1852–1857. [PubMed] [Google Scholar]
  51. Sweder K. S. Nucleotide excision repair in yeast. Curr Genet. 1994 Dec;27(1):1–16. doi: 10.1007/BF00326572. [DOI] [PubMed] [Google Scholar]
  52. Takao M., Abramic M., Moos M., Jr, Otrin V. R., Wootton J. C., McLenigan M., Levine A. S., Protic M. A 127 kDa component of a UV-damaged DNA-binding complex, which is defective in some xeroderma pigmentosum group E patients, is homologous to a slime mold protein. Nucleic Acids Res. 1993 Aug 25;21(17):4111–4118. doi: 10.1093/nar/21.17.4111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Tanaka K., Wood R. D. Xeroderma pigmentosum and nucleotide excision repair of DNA. Trends Biochem Sci. 1994 Feb;19(2):83–86. doi: 10.1016/0968-0004(94)90040-X. [DOI] [PubMed] [Google Scholar]
  54. Thiery R., Robbins S., Khosla M., Spiegelman G. B., Weeks G. The effects of expression of an activated rasG mutation on the differentiation of Dictyostelium. Biochem Cell Biol. 1992 Oct-Nov;70(10-11):1193–1199. doi: 10.1139/o92-165. [DOI] [PubMed] [Google Scholar]
  55. Van Houten B., McCullough A. Nucleotide excision repair in E. coli. Ann N Y Acad Sci. 1994 Jul 29;726:236–251. doi: 10.1111/j.1749-6632.1994.tb52822.x. [DOI] [PubMed] [Google Scholar]
  56. Walker G. C. Inducible DNA repair systems. Annu Rev Biochem. 1985;54:425–457. doi: 10.1146/annurev.bi.54.070185.002233. [DOI] [PubMed] [Google Scholar]
  57. 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]
  58. van Vuuren A. J., Vermeulen W., Ma L., Weeda G., Appeldoorn E., Jaspers N. G., van der Eb A. J., Bootsma D., Hoeijmakers J. H., Humbert S. Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH). EMBO J. 1994 Apr 1;13(7):1645–1653. doi: 10.1002/j.1460-2075.1994.tb06428.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES