Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1996 Jun 15;24(12):2295–2301. doi: 10.1093/nar/24.12.2295

repE--the Dictyostelium homolog of the human xeroderma pigmentosum group E gene is developmentally regulated and contains a leucine zipper motif.

H Alexander 1, S K Lee 1, S L Yu 1, S Alexander 1
PMCID: PMC145941  PMID: 8710499

Abstract

We have cloned and characterized the Dictyostelium discoideum repE gene, a homolog of the human xeroderma pigmentosum (XP) group E gene which encodes a UV-damaged DNA binding protein. The repE gene maps to chromosome 4 and it is the first gene identified in Dictyostelium that is homologous to those involved in nucleotide excision repair and their related XP diseases in humans. The predicted protein encodes a leucine zipper motif. The repE gene is not expressed by mitotically dividing cells, and repE mRNA is first detected during the aggregation phase of development when the cells have ceased dividing and replicating genomic DNA. The mRNA level plateaus by the time the developing cells have entered multicellular aggregates and remains at the same steady-state level for the remainder of development. In addition, we have demonstrated that the level of mRNA is very low in developing cells. These observations suggest that repE may play a regulatory role in development. The data indicate that potential developmental roles for XP-related genes can be profitably studied in this system.

Full Text

The Full Text of this article is available as a PDF (121.1 KB).

Selected References

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

  1. Abel T., Maniatis T. Gene regulation. Action of leucine zippers. Nature. 1989 Sep 7;341(6237):24–25. doi: 10.1038/341024a0. [DOI] [PubMed] [Google Scholar]
  2. Aboussekhra A., Biggerstaff M., Shivji M. K., Vilpo J. A., Moncollin V., Podust V. N., Protić M., Hübscher U., Egly J. M., Wood R. D. Mammalian DNA nucleotide excision repair reconstituted with purified protein components. Cell. 1995 Mar 24;80(6):859–868. doi: 10.1016/0092-8674(95)90289-9. [DOI] [PubMed] [Google Scholar]
  3. Albright C. F., Robbins R. W. The sequence and transcript heterogeneity of the yeast gene ALG1, an essential mannosyltransferase involved in N-glycosylation. J Biol Chem. 1990 Apr 25;265(12):7042–7049. [PubMed] [Google Scholar]
  4. Alexander H., Alexander S. Identification of introns by reverse-transcription PCR. Biotechniques. 1996 May;20(5):778–780. doi: 10.2144/96205bm08. [DOI] [PubMed] [Google Scholar]
  5. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  6. Ashley C. T., Jr, Warren S. T. Trinucleotide repeat expansion and human disease. Annu Rev Genet. 1995;29:703–728. doi: 10.1146/annurev.ge.29.120195.003415. [DOI] [PubMed] [Google Scholar]
  7. Blusch J., Alexander S., Nellen W. Multiple signal transduction pathways regulate discoidin I gene expression in Dictyostelium discoideum. Differentiation. 1995 Apr;58(4):253–260. doi: 10.1046/j.1432-0436.1995.5840253.x. [DOI] [PubMed] [Google Scholar]
  8. Brunk B. P., Adler P. N. The sequence of the Drosophila regulatory gene Suppressor two of zeste. Nucleic Acids Res. 1991 Jun 11;19(11):3149–3149. doi: 10.1093/nar/19.11.3149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cheesman S., McAleese S., Goman M., Johnson D., Horrocks P., Ridley R. G., Kilbey B. J. The gene encoding topoisomerase II from Plasmodium falciparum. Nucleic Acids Res. 1994 Jul 11;22(13):2547–2551. doi: 10.1093/nar/22.13.2547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Demerec M., Adelberg E. A., Clark A. J., Hartman P. E. A proposal for a uniform nomenclature in bacterial genetics. Genetics. 1966 Jul;54(1):61–76. doi: 10.1093/genetics/54.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Dualan R., Brody T., Keeney S., Nichols A. F., Admon A., Linn S. Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein. Genomics. 1995 Sep 1;29(1):62–69. doi: 10.1006/geno.1995.1215. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Fox B. A., Li W. B., Tanaka M., Inselburg J., Bzik D. J. Molecular characterization of the largest subunit of Plasmodium falciparum RNA polymerase I. Mol Biochem Parasitol. 1993 Sep;61(1):37–48. doi: 10.1016/0166-6851(93)90156-r. [DOI] [PubMed] [Google Scholar]
  16. Halfter H., Kavety B., Vandekerckhove J., Kiefer F., Gallwitz D. Sequence, expression and mutational analysis of BAF1, a transcriptional activator and ARS1-binding protein of the yeast Saccharomyces cerevisiae. EMBO J. 1989 Dec 20;8(13):4265–4272. doi: 10.1002/j.1460-2075.1989.tb08612.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hanawalt P. C. Transcription-coupled repair and human disease. Science. 1994 Dec 23;266(5193):1957–1958. doi: 10.1126/science.7801121. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. He Z., Henricksen L. A., Wold M. S., Ingles C. J. RPA involvement in the damage-recognition and incision steps of nucleotide excision repair. Nature. 1995 Apr 6;374(6522):566–569. doi: 10.1038/374566a0. [DOI] [PubMed] [Google Scholar]
  20. Higgins D. R., Prakash S., Reynolds P., Polakowska R., Weber S., Prakash L. Isolation and characterization of the RAD3 gene of Saccharomyces cerevisiae and inviability of rad3 deletion mutants. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5680–5684. doi: 10.1073/pnas.80.18.5680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hoeijmakers J. H. Nucleotide excision repair I: from E. coli to yeast. Trends Genet. 1993 May;9(5):173–177. doi: 10.1016/0168-9525(93)90164-d. [DOI] [PubMed] [Google Scholar]
  22. Hwang B. J., Liao J. C., Chu G. Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in xeroderma pigmentosum group E cells. Mutat Res. 1996 Jan 2;362(1):105–117. doi: 10.1016/0921-8777(95)00040-2. [DOI] [PubMed] [Google Scholar]
  23. Johnson P. F., McKnight S. L. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989;58:799–839. doi: 10.1146/annurev.bi.58.070189.004055. [DOI] [PubMed] [Google Scholar]
  24. Keeney S., Chang G. J., Linn S. Characterization of a human DNA damage binding protein implicated in xeroderma pigmentosum E. J Biol Chem. 1993 Oct 5;268(28):21293–21300. [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Kuspa A., Maghakian D., Bergesch P., Loomis W. F. Physical mapping of genes to specific chromosomes in Dictyostelium discoideum. Genomics. 1992 May;13(1):49–61. doi: 10.1016/0888-7543(92)90201-3. [DOI] [PubMed] [Google Scholar]
  28. Lacombe M. L., Podgorski G. J., Franke J., Kessin R. H. Molecular cloning and developmental expression of the cyclic nucleotide phosphodiesterase gene of Dictyostelium discoideum. J Biol Chem. 1986 Dec 25;261(36):16811–16817. [PubMed] [Google Scholar]
  29. Lee S. H., Kim D. K., Drissi R. Human xeroderma pigmentosum group A protein interacts with human replication protein A and inhibits DNA replication. J Biol Chem. 1995 Sep 15;270(37):21800–21805. doi: 10.1074/jbc.270.37.21800. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Li L., Lu X., Peterson C. A., Legerski R. J. An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair. Mol Cell Biol. 1995 Oct;15(10):5396–5402. doi: 10.1128/mcb.15.10.5396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Li W. B., Bzik D. J., Tanaka M., Gu H. M., Fox B. A., Inselburg J. Characterization of the gene encoding the largest subunit of Plasmodium falciparum RNA polymerase III. Mol Biochem Parasitol. 1991 Jun;46(2):229–239. doi: 10.1016/0166-6851(91)90047-a. [DOI] [PubMed] [Google Scholar]
  33. Lommel L., Hanawalt P. C. The genetic defect in the Chinese hamster ovary cell mutant UV61 permits moderate selective repair of cyclobutane pyrimidine dimers in an expressed gene. Mutat Res. 1991 Sep;255(2):183–191. doi: 10.1016/0921-8777(91)90052-q. [DOI] [PubMed] [Google Scholar]
  34. Loomis W. F., Welker D., Hughes J., Maghakian D., Kuspa A. Integrated maps of the chromosomes in Dictyostelium discoideum. Genetics. 1995 Sep;141(1):147–157. doi: 10.1093/genetics/141.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Mellon I., Hanawalt P. C. Induction of the Escherichia coli lactose operon selectively increases repair of its transcribed DNA strand. Nature. 1989 Nov 2;342(6245):95–98. doi: 10.1038/342095a0. [DOI] [PubMed] [Google Scholar]
  37. Mounkes L. C., Jones R. S., Liang B. C., Gelbart W., Fuller M. T. A Drosophila model for xeroderma pigmentosum and Cockayne's syndrome: haywire encodes the fly homolog of ERCC3, a human excision repair gene. Cell. 1992 Dec 11;71(6):925–937. doi: 10.1016/0092-8674(92)90389-t. [DOI] [PubMed] [Google Scholar]
  38. O'Hara P. J., Horowitz H., Eichinger G., Young E. T. The yeast ADR6 gene encodes homopolymeric amino acid sequences and a potential metal-binding domain. Nucleic Acids Res. 1988 Nov 11;16(21):10153–10169. doi: 10.1093/nar/16.21.10153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Okuno Y., Tateishi S., Yamaizumi M. Complementation of xeroderma pigmentosum cells by microinjection of mRNA fractionated under denaturing conditions: an estimation of sizes of XP-E and XP-G mRNA. Mutat Res. 1994 Jan;314(1):11–19. doi: 10.1016/0921-8777(94)90056-6. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Reardon J. T., Nichols A. F., Keeney S., Smith C. A., Taylor J. S., Linn S., Sancar A. Comparative analysis of binding of human damaged DNA-binding protein (XPE) and Escherichia coli damage recognition protein (UvrA) to the major ultraviolet photoproducts: T[c,s]T, T[t,s]T, T[6-4]T, and T[Dewar]T. J Biol Chem. 1993 Oct 5;268(28):21301–21308. [PubMed] [Google Scholar]
  42. Sancar G. B., Siede W., van Zeeland A. A. Repair and processing of DNA damage: a summary of recent progress. Mutat Res. 1996 Jan 2;362(1):127–146. doi: 10.1016/0921-8777(95)00029-1. [DOI] [PubMed] [Google Scholar]
  43. Schiestl R. H., Prakash S. RAD10, an excision repair gene of Saccharomyces cerevisiae, is involved in the RAD1 pathway of mitotic recombination. Mol Cell Biol. 1990 Jun;10(6):2485–2491. doi: 10.1128/mcb.10.6.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schnitzler G. R., Fischer W. H., Firtel R. A. Cloning and characterization of the G-box binding factor, an essential component of the developmental switch between early and late development in Dictyostelium. Genes Dev. 1994 Feb 15;8(4):502–514. doi: 10.1101/gad.8.4.502. [DOI] [PubMed] [Google Scholar]
  45. Sekelsky J. J., McKim K. S., Chin G. M., Hawley R. S. The Drosophila meiotic recombination gene mei-9 encodes a homologue of the yeast excision repair protein Rad1. Genetics. 1995 Oct;141(2):619–627. doi: 10.1093/genetics/141.2.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Shaulsky G., Kuspa A., Loomis W. F. A multidrug resistance transporter/serine protease gene is required for prestalk specialization in Dictyostelium. Genes Dev. 1995 May 1;9(9):1111–1122. doi: 10.1101/gad.9.9.1111. [DOI] [PubMed] [Google Scholar]
  47. Stott K., Blackburn J. M., Butler P. J., Perutz M. Incorporation of glutamine repeats makes protein oligomerize: implications for neurodegenerative diseases. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6509–6513. doi: 10.1073/pnas.92.14.6509. [DOI] [PMC free article] [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. 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]
  52. Treiber D. K., Chen Z., Essigmann J. M. An ultraviolet light-damaged DNA recognition protein absent in xeroderma pigmentosum group E cells binds selectively to pyrimidine (6-4) pyrimidone photoproducts. Nucleic Acids Res. 1992 Nov 11;20(21):5805–5810. doi: 10.1093/nar/20.21.5805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Venema J., Mullenders L. H., Natarajan A. T., van Zeeland A. A., Mayne L. V. The genetic defect in Cockayne syndrome is associated with a defect in repair of UV-induced DNA damage in transcriptionally active DNA. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4707–4711. doi: 10.1073/pnas.87.12.4707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Warrick H. M., Spudich J. A. Codon preference in Dictyostelium discoideum. Nucleic Acids Res. 1988 Jul 25;16(14A):6617–6635. doi: 10.1093/nar/16.14.6617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Zeng X. R., Jiang Y., Zhang S. J., Hao H., Lee M. Y. DNA polymerase delta is involved in the cellular response to UV damage in human cells. J Biol Chem. 1994 May 13;269(19):13748–13751. [PubMed] [Google Scholar]
  56. 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