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. 1995 Nov;15(11):6256–6261. doi: 10.1128/mcb.15.11.6256

The transcriptionally competent U2 gene is necessary and sufficient for adenovirus type 12 induction of the fragile site at 17q21-22.

S Gargano 1, P Wang 1, E Rusanganwa 1, S Bacchetti 1
PMCID: PMC230877  PMID: 7565778

Abstract

Adenovirus type 12 induces four fragile sites upon infection of human cells. The U2 locus, consisting of up to 20 tandem repeats of a 5.8-kbp monomer, maps at the most sensitive of these sites at 17q21-22. We have previously shown that an artificial U2 locus integrated into the human genome generates a new virus-induced fragile site. To determine which elements within the U2 monomer are responsible for fragility, we constructed loci consisting of tandem repeats of subfragments of the U2 monomer. With this approach, we demonstrate that a transcriptionally competent U2 gene is necessary and sufficient for virus-induced fragility and that no other element within the 5.8-kbp monomer contributes to this effect.

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Selected References

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  1. Bailey A. D., Li Z., Pavelitz T., Weiner A. M. Adenovirus type 12-induced fragility of the human RNU2 locus requires U2 small nuclear RNA transcriptional regulatory elements. Mol Cell Biol. 1995 Nov;15(11):6246–6255. doi: 10.1128/mcb.15.11.6246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bossone S. A., Asselin C., Patel A. J., Marcu K. B. MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7452–7456. doi: 10.1073/pnas.89.16.7452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Busch H., Reddy R., Rothblum L., Choi Y. C. SnRNAs, SnRNPs, and RNA processing. Annu Rev Biochem. 1982;51:617–654. doi: 10.1146/annurev.bi.51.070182.003153. [DOI] [PubMed] [Google Scholar]
  4. Caporossi D., Bacchetti S. Definition of adenovirus type 5 functions involved in the induction of chromosomal aberrations in human cells. J Gen Virol. 1990 Apr;71(Pt 4):801–808. doi: 10.1099/0022-1317-71-4-801. [DOI] [PubMed] [Google Scholar]
  5. Caporossi D., Bacchetti S., Nicoletti B. Synergism between aphidicolin and adenoviruses in the induction of breaks at fragile sites on human chromosomes. Cancer Genet Cytogenet. 1991 Jul 1;54(1):39–53. doi: 10.1016/0165-4608(91)90028-s. [DOI] [PubMed] [Google Scholar]
  6. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Durnam D. M., Menninger J. C., Chandler S. H., Smith P. P., McDougall J. K. A fragile site in the human U2 small nuclear RNA gene cluster is revealed by adenovirus type 12 infection. Mol Cell Biol. 1988 May;8(5):1863–1867. doi: 10.1128/mcb.8.5.1863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goessens G. Nucleolar structure. Int Rev Cytol. 1984;87:107–158. doi: 10.1016/s0074-7696(08)62441-9. [DOI] [PubMed] [Google Scholar]
  9. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  10. Hammarström K., Santesson B., Westin G., Pettersson U. The gene cluster for human U2 RNA is located on chromosome 17q21. Exp Cell Res. 1985 Aug;159(2):473–478. doi: 10.1016/s0014-4827(85)80020-3. [DOI] [PubMed] [Google Scholar]
  11. Hansen R. S., Canfield T. K., Lamb M. M., Gartler S. M., Laird C. D. Association of fragile X syndrome with delayed replication of the FMR1 gene. Cell. 1993 Jul 2;73(7):1403–1409. doi: 10.1016/0092-8674(93)90365-w. [DOI] [PubMed] [Google Scholar]
  12. Hecht F. Fragile sites, cancer chromosome breakpoints, and oncogenes all cluster in light G bands. Cancer Genet Cytogenet. 1988 Mar;31(1):17–24. doi: 10.1016/0165-4608(88)90005-2. [DOI] [PubMed] [Google Scholar]
  13. Janson L., Weller P., Pettersson U. Nuclear factor I can functionally replace transcription factor Sp1 in a U2 small nuclear RNA gene enhancer. J Mol Biol. 1989 Jan 20;205(2):387–396. doi: 10.1016/0022-2836(89)90349-5. [DOI] [PubMed] [Google Scholar]
  14. Kennedy G. C., Rutter W. J. Pur-1, a zinc-finger protein that binds to purine-rich sequences, transactivates an insulin promoter in heterologous cells. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11498–11502. doi: 10.1073/pnas.89.23.11498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Knight S. J., Flannery A. V., Hirst M. C., Campbell L., Christodoulou Z., Phelps S. R., Pointon J., Middleton-Price H. R., Barnicoat A., Pembrey M. E. Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell. 1993 Jul 16;74(1):127–134. doi: 10.1016/0092-8674(93)90300-f. [DOI] [PubMed] [Google Scholar]
  16. Lawler S. H., Jones R. W., Eliceiri B. P., Eliceiri G. L. Adenovirus infection retards ribosomal RNA processing. J Cell Physiol. 1989 Jan;138(1):205–207. doi: 10.1002/jcp.1041380127. [DOI] [PubMed] [Google Scholar]
  17. Li Y. P., Tomanin R., Smiley J. R., Bacchetti S. Generation of a new adenovirus type 12-inducible fragile site by insertion of an artificial U2 locus in the human genome. Mol Cell Biol. 1993 Oct;13(10):6064–6070. doi: 10.1128/mcb.13.10.6064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lindgren V., Ares M., Jr, Weiner A. M., Francke U. Human genes for U2 small nuclear RNA map to a major adenovirus 12 modification site on chromosome 17. Nature. 1985 Mar 7;314(6006):115–116. doi: 10.1038/314115a0. [DOI] [PubMed] [Google Scholar]
  19. Lindgren V., Bernstein L. B., Weiner A. M., Francke U. Human U1 small nuclear RNA pseudogenes do not map to the site of the U1 genes in 1p36 but are clustered in 1q12-q22. Mol Cell Biol. 1985 Sep;5(9):2172–2180. doi: 10.1128/mcb.5.9.2172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lu Q., Wallrath L. L., Granok H., Elgin S. C. (CT)n (GA)n repeats and heat shock elements have distinct roles in chromatin structure and transcriptional activation of the Drosophila hsp26 gene. Mol Cell Biol. 1993 May;13(5):2802–2814. doi: 10.1128/mcb.13.5.2802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mangin M., Ares M., Jr, Weiner A. M. Human U2 small nuclear RNA genes contain an upstream enhancer. EMBO J. 1986 May;5(5):987–995. doi: 10.1002/j.1460-2075.1986.tb04313.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McDougall J. K. Adenovirus-induced chromosome aberrations in human cells. J Gen Virol. 1971 Jul;12(1):43–51. doi: 10.1099/0022-1317-12-1-43. [DOI] [PubMed] [Google Scholar]
  23. Nancarrow J. K., Kremer E., Holman K., Eyre H., Doggett N. A., Le Paslier D., Callen D. F., Sutherland G. R., Richards R. I. Implications of FRA16A structure for the mechanism of chromosomal fragile site genesis. Science. 1994 Jun 24;264(5167):1938–1941. doi: 10.1126/science.8009225. [DOI] [PubMed] [Google Scholar]
  24. Naylor S. L., Zabel B. U., Manser T., Gesteland R., Sakaguchi A. Y. Localization of human U1 small nuclear RNA genes to band p36.3 of chromosome 1 by in situ hybridization. Somat Cell Mol Genet. 1984 May;10(3):307–313. doi: 10.1007/BF01535252. [DOI] [PubMed] [Google Scholar]
  25. Panning B., Smiley J. R. Activation of RNA polymerase III transcription of human Alu repetitive elements by adenovirus type 5: requirement for the E1b 58-kilodalton protein and the products of E4 open reading frames 3 and 6. Mol Cell Biol. 1993 Jun;13(6):3231–3244. doi: 10.1128/mcb.13.6.3231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Parrish J. E., Oostra B. A., Verkerk A. J., Richards C. S., Reynolds J., Spikes A. S., Shaffer L. G., Nelson D. L. Isolation of a GCC repeat showing expansion in FRAXF, a fragile site distal to FRAXA and FRAXE. Nat Genet. 1994 Nov;8(3):229–235. doi: 10.1038/ng1194-229. [DOI] [PubMed] [Google Scholar]
  27. Pavelitz T., Rusché L., Matera A. G., Scharf J. M., Weiner A. M. Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ, without changing the cytological context of the RNU2 locus. EMBO J. 1995 Jan 3;14(1):169–177. doi: 10.1002/j.1460-2075.1995.tb06987.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rasheed S., Nelson-Rees W. A., Toth E. M., Arnstein P., Gardner M. B. Characterization of a newly derived human sarcoma cell line (HT-1080). Cancer. 1974 Apr;33(4):1027–1033. doi: 10.1002/1097-0142(197404)33:4<1027::aid-cncr2820330419>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  29. STICH H. F., VANHOOSIER G. L., TRENTIN J. J. VIRUSES AND MAMMALIAN CHROMOSOMES; CHROMOSOME ABERRATIONS BY HUMAN ADENOVIRUS TYPE 12. Exp Cell Res. 1964 Apr;34:400–403. doi: 10.1016/0014-4827(64)90375-1. [DOI] [PubMed] [Google Scholar]
  30. Schramayr S., Caporossi D., Mak I., Jelinek T., Bacchetti S. Chromosomal damage induced by human adenovirus type 12 requires expression of the E1B 55-kilodalton viral protein. J Virol. 1990 May;64(5):2090–2095. doi: 10.1128/jvi.64.5.2090-2095.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  32. Steffensen D. M., Szabo P., McDougall J. K. Adenovirus 12 uncoiler regions of human chromosome 1 in relation to the 5S rRNA genes. Exp Cell Res. 1976 Jul;100(2):436–439. doi: 10.1016/0014-4827(76)90176-2. [DOI] [PubMed] [Google Scholar]
  33. Tsukiyama T., Becker P. B., Wu C. ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature. 1994 Feb 10;367(6463):525–532. doi: 10.1038/367525a0. [DOI] [PubMed] [Google Scholar]
  34. Van Arsdell S. W., Weiner A. M. Human genes for U2 small nuclear RNA are tandemly repeated. Mol Cell Biol. 1984 Mar;4(3):492–499. doi: 10.1128/mcb.4.3.492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Westin G., Zabielski J., Hammarström K., Monstein H. J., Bark C., Pettersson U. Clustered genes for human U2 RNA. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3811–3815. doi: 10.1073/pnas.81.12.3811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yunis J. J. Chromosomal rearrangements, genes, and fragile sites in cancer: clinical and biologic implications. Important Adv Oncol. 1986:93–128. [PubMed] [Google Scholar]
  37. Yunis J. J., Soreng A. L., Bowe A. E. Fragile sites are targets of diverse mutagens and carcinogens. Oncogene. 1987 Mar;1(1):59–69. [PubMed] [Google Scholar]
  38. Zur Hausen H. Induction of specific chromosomal aberrations by adenovirus type 12 in human embryonic kidney cells. J Virol. 1967 Dec;1(6):1174–1185. doi: 10.1128/jvi.1.6.1174-1185.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]

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