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. 1992 May;66(5):3140–3150. doi: 10.1128/jvi.66.5.3140-3150.1992

Nuclear factor I is specifically targeted to discrete subnuclear sites in adenovirus type 2-infected cells.

J Bosher 1, A Dawson 1, R T Hay 1
PMCID: PMC241077  PMID: 1560540

Abstract

During the S phase of the eukaryotic cell cycle and in virus-infected cells, DNA replication takes place at discrete sites in the nucleus, although it is not clear how the proteins involved in the replicative process are directed to these sites. Nuclear factor I is a cellular, sequence-specific DNA-binding protein utilized by adenovirus type 2 to facilitate the assembly of a nucleoprotein complex at the viral origin of DNA replication. Immunofluorescence experiments reveal that in uninfected cells, nuclear factor I is distributed evenly throughout the nucleus. However, after a cell is infected with adenovirus type 2, the distribution of nuclear factor I is dramatically altered, being colocalized with the viral DNA-binding protein in a limited number of subnuclear sites which bromodeoxyuridine pulse-labeling experiments have identified as sites of viral DNA replication. Experiments with adenovirus type 4, which does not require nuclear factor I for viral DNA replication, indicate that although the adenovirus type 4 DNA-binding protein is localized to discrete nuclear sites, this does not result in the redistribution of nuclear factor I. Localization of nuclear factor I to discrete subnuclear sites is therefore likely to represent a specific targeting event that reflects the requirement for nuclear factor I in adenovirus type 2 DNA replication.

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Selected References

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

  1. Adhya S., Shneidman P. S., Hurwitz J. Reconstruction of adenovirus replication origins with a human nuclear factor I binding site. J Biol Chem. 1986 Mar 5;261(7):3339–3346. [PubMed] [Google Scholar]
  2. Berezney R., Coffey D. S. Nuclear protein matrix: association with newly synthesized DNA. Science. 1975 Jul 25;189(4199):291–293. doi: 10.1126/science.1145202. [DOI] [PubMed] [Google Scholar]
  3. Bosher J., Leith I. R., Temperley S. M., Wells M., Hay R. T. The DNA-binding domain of nuclear factor I is sufficient to cooperate with the adenovirus type 2 DNA-binding protein in viral DNA replication. J Gen Virol. 1991 Dec;72(Pt 12):2975–2980. doi: 10.1099/0022-1317-72-12-2975. [DOI] [PubMed] [Google Scholar]
  4. Bosher J., Robinson E. C., Hay R. T. Interactions between the adenovirus type 2 DNA polymerase and the DNA binding domain of nuclear factor I. New Biol. 1990 Dec;2(12):1083–1090. [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  6. Bravo R., Macdonald-Bravo H. Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites. J Cell Biol. 1987 Oct;105(4):1549–1554. doi: 10.1083/jcb.105.4.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Celis J. E., Madsen P., Celis A., Nielsen H. V., Gesser B. Cyclin (PCNA, auxiliary protein of DNA polymerase delta) is a central component of the pathway(s) leading to DNA replication and cell division. FEBS Lett. 1987 Aug 10;220(1):1–7. doi: 10.1016/0014-5793(87)80865-7. [DOI] [PubMed] [Google Scholar]
  8. Challberg M. D., Kelly T. J. Animal virus DNA replication. Annu Rev Biochem. 1989;58:671–717. doi: 10.1146/annurev.bi.58.070189.003323. [DOI] [PubMed] [Google Scholar]
  9. Challberg M. D., Rawlins D. R. Template requirements for the initiation of adenovirus DNA replication. Proc Natl Acad Sci U S A. 1984 Jan;81(1):100–104. doi: 10.1073/pnas.81.1.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chen M., Mermod N., Horwitz M. S. Protein-protein interactions between adenovirus DNA polymerase and nuclear factor I mediate formation of the DNA replication preinitiation complex. J Biol Chem. 1990 Oct 25;265(30):18634–18642. [PubMed] [Google Scholar]
  11. Cleat P. H., Hay R. T. Co-operative interactions between NFI and the adenovirus DNA binding protein at the adenovirus origin of replication. EMBO J. 1989 Jun;8(6):1841–1848. doi: 10.1002/j.1460-2075.1989.tb03579.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dingwall C. Transport across the nuclear envelope: enigmas and explanations. Bioessays. 1991 May;13(5):213–218. doi: 10.1002/bies.950130503. [DOI] [PubMed] [Google Scholar]
  13. Fox M. H., Arndt-Jovin D. J., Jovin T. M., Baumann P. H., Robert-Nicoud M. Spatial and temporal distribution of DNA replication sites localized by immunofluorescence and confocal microscopy in mouse fibroblasts. J Cell Sci. 1991 Jun;99(Pt 2):247–253. doi: 10.1242/jcs.99.2.247. [DOI] [PubMed] [Google Scholar]
  14. Ghosh S., Gifford A. M., Riviere L. R., Tempst P., Nolan G. P., Baltimore D. Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal. Cell. 1990 Sep 7;62(5):1019–1029. doi: 10.1016/0092-8674(90)90276-k. [DOI] [PubMed] [Google Scholar]
  15. Gounari F., De Francesco R., Schmitt J., van der Vliet P., Cortese R., Stunnenberg H. Amino-terminal domain of NF1 binds to DNA as a dimer and activates adenovirus DNA replication. EMBO J. 1990 Feb;9(2):559–566. doi: 10.1002/j.1460-2075.1990.tb08143.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Guggenheimer R. A., Stillman B. W., Nagata K., Tamanoi F., Hurwitz J. DNA sequences required for the in vitro replication of adenovirus DNA. Proc Natl Acad Sci U S A. 1984 May;81(10):3069–3073. doi: 10.1073/pnas.81.10.3069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hand R. Eucaryotic DNA: organization of the genome for replication. Cell. 1978 Oct;15(2):317–325. doi: 10.1016/0092-8674(78)90001-6. [DOI] [PubMed] [Google Scholar]
  18. Harris M. P., Hay R. T. DNA sequences required for the initiation of adenovirus type 4 DNA replication in vitro. J Mol Biol. 1988 May 5;201(1):57–67. doi: 10.1016/0022-2836(88)90438-x. [DOI] [PubMed] [Google Scholar]
  19. Hay R. T., McDougall I. M. Viable viruses with deletions in the left inverted terminal repeat define the adenovirus origin of DNA replication. J Gen Virol. 1986 Feb;67(Pt 2):321–332. doi: 10.1099/0022-1317-67-2-321. [DOI] [PubMed] [Google Scholar]
  20. Hay R. T. Origin of adenovirus DNA replication. Role of the nuclear factor I binding site in vivo. J Mol Biol. 1985 Nov 5;186(1):129–136. doi: 10.1016/0022-2836(85)90263-3. [DOI] [PubMed] [Google Scholar]
  21. Hay R. T., Russell W. C. Recognition mechanisms in the synthesis of animal virus DNA. Biochem J. 1989 Feb 15;258(1):3–16. doi: 10.1042/bj2580003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hay R. T. The origin of adenovirus DNA replication: minimal DNA sequence requirement in vivo. EMBO J. 1985 Feb;4(2):421–426. doi: 10.1002/j.1460-2075.1985.tb03645.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hayashi K., Russell W. C. A study of the development of adenovirus antigens by the immunofluorescent technique. Virology. 1968 Mar;34(3):470–480. doi: 10.1016/0042-6822(68)90067-6. [DOI] [PubMed] [Google Scholar]
  24. Jackson D. A., Cook P. R. Replication occurs at a nucleoskeleton. EMBO J. 1986 Jun;5(6):1403–1410. doi: 10.1002/j.1460-2075.1986.tb04374.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jones K. A., Kadonaga J. T., Rosenfeld P. J., Kelly T. J., Tjian R. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987 Jan 16;48(1):79–89. doi: 10.1016/0092-8674(87)90358-8. [DOI] [PubMed] [Google Scholar]
  26. Kenny M. K., Hurwitz J. Initiation of adenovirus DNA replication. II. Structural requirements using synthetic oligonucleotide adenovirus templates. J Biol Chem. 1988 Jul 15;263(20):9809–9817. [PubMed] [Google Scholar]
  27. Kieran M., Blank V., Logeat F., Vandekerckhove J., Lottspeich F., Le Bail O., Urban M. B., Kourilsky P., Baeuerle P. A., Israël A. The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product. Cell. 1990 Sep 7;62(5):1007–1018. doi: 10.1016/0092-8674(90)90275-j. [DOI] [PubMed] [Google Scholar]
  28. Knox J. J., Rebstein P. J., Manoukian A., Gronostajski R. M. In vivo stimulation of a chimeric promoter by binding sites for nuclear factor I. Mol Cell Biol. 1991 Jun;11(6):2946–2951. doi: 10.1128/mcb.11.6.2946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lally C., Dörper T., Gröger W., Antoine G., Winnacker E. L. A size analysis of the adenovirus replicon. EMBO J. 1984 Feb;3(2):333–337. doi: 10.1002/j.1460-2075.1984.tb01807.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lindenbaum J. O., Field J., Hurwitz J. The adenovirus DNA binding protein and adenovirus DNA polymerase interact to catalyze elongation of primed DNA templates. J Biol Chem. 1986 Aug 5;261(22):10218–10227. [PubMed] [Google Scholar]
  31. Meisterernst M., Rogge L., Foeckler R., Karaghiosoff M., Winnacker E. L. Structural and functional organization of a porcine gene coding for nuclear factor I. Biochemistry. 1989 Oct 3;28(20):8191–8200. doi: 10.1021/bi00446a034. [DOI] [PubMed] [Google Scholar]
  32. Mermod N., O'Neill E. A., Kelly T. J., Tjian R. The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell. 1989 Aug 25;58(4):741–753. doi: 10.1016/0092-8674(89)90108-6. [DOI] [PubMed] [Google Scholar]
  33. Mills A. D., Blow J. J., White J. G., Amos W. B., Wilcock D., Laskey R. A. Replication occurs at discrete foci spaced throughout nuclei replicating in vitro. J Cell Sci. 1989 Nov;94(Pt 3):471–477. doi: 10.1242/jcs.94.3.471. [DOI] [PubMed] [Google Scholar]
  34. Moen P. T., Jr, Fox E., Bodnar J. W. Adenovirus and minute virus of mice DNAs are localized at the nuclear periphery. Nucleic Acids Res. 1990 Feb 11;18(3):513–520. doi: 10.1093/nar/18.3.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mul Y. M., Verrijzer C. P., van der Vliet P. C. Transcription factors NFI and NFIII/oct-1 function independently, employing different mechanisms to enhance adenovirus DNA replication. J Virol. 1990 Nov;64(11):5510–5518. doi: 10.1128/jvi.64.11.5510-5518.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nagata K., Guggenheimer R. A., Hurwitz J. Specific binding of a cellular DNA replication protein to the origin of replication of adenovirus DNA. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6177–6181. doi: 10.1073/pnas.80.20.6177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Nakamura H., Morita T., Masaki S., Yoshida S. Intracellular localization and metabolism of DNA polymerase alpha in human cells visualized with monoclonal antibody. Exp Cell Res. 1984 Mar;151(1):123–133. doi: 10.1016/0014-4827(84)90362-8. [DOI] [PubMed] [Google Scholar]
  38. Nakamura H., Morita T., Sato C. Structural organizations of replicon domains during DNA synthetic phase in the mammalian nucleus. Exp Cell Res. 1986 Aug;165(2):291–297. doi: 10.1016/0014-4827(86)90583-5. [DOI] [PubMed] [Google Scholar]
  39. Nakayasu H., Berezney R. Mapping replicational sites in the eucaryotic cell nucleus. J Cell Biol. 1989 Jan;108(1):1–11. doi: 10.1083/jcb.108.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. O'Neill E. A., Kelly T. J. Purification and characterization of nuclear factor III (origin recognition protein C), a sequence-specific DNA binding protein required for efficient initiation of adenovirus DNA replication. J Biol Chem. 1988 Jan 15;263(2):931–937. [PubMed] [Google Scholar]
  41. Paonessa G., Gounari F., Frank R., Cortese R. Purification of a NF1-like DNA-binding protein from rat liver and cloning of the corresponding cDNA. EMBO J. 1988 Oct;7(10):3115–3123. doi: 10.1002/j.1460-2075.1988.tb03178.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Pardoll D. M., Vogelstein B., Coffey D. S. A fixed site of DNA replication in eucaryotic cells. Cell. 1980 Feb;19(2):527–536. doi: 10.1016/0092-8674(80)90527-9. [DOI] [PubMed] [Google Scholar]
  43. Pruijn G. J., van Driel W., van der Vliet P. C. Nuclear factor III, a novel sequence-specific DNA-binding protein from HeLa cells stimulating adenovirus DNA replication. Nature. 1986 Aug 14;322(6080):656–659. doi: 10.1038/322656a0. [DOI] [PubMed] [Google Scholar]
  44. Quinlan M. P., Chen L. B., Knipe D. M. The intranuclear location of a herpes simplex virus DNA-binding protein is determined by the status of viral DNA replication. Cell. 1984 Apr;36(4):857–868. doi: 10.1016/0092-8674(84)90035-7. [DOI] [PubMed] [Google Scholar]
  45. Randall R. E., Dinwoodie N. Intranuclear localization of herpes simplex virus immediate-early and delayed-early proteins: evidence that ICP 4 is associated with progeny virus DNA. J Gen Virol. 1986 Oct;67(Pt 10):2163–2177. doi: 10.1099/0022-1317-67-10-2163. [DOI] [PubMed] [Google Scholar]
  46. Rawlins D. R., Rosenfeld P. J., Wides R. J., Challberg M. D., Kelly T. J., Jr Structure and function of the adenovirus origin of replication. Cell. 1984 May;37(1):309–319. doi: 10.1016/0092-8674(84)90327-1. [DOI] [PubMed] [Google Scholar]
  47. Reich N. C., Sarnow P., Duprey E., Levine A. J. Monoclonal antibodies which recognize native and denatured forms of the adenovirus DNA-binding protein. Virology. 1983 Jul 30;128(2):480–484. doi: 10.1016/0042-6822(83)90274-x. [DOI] [PubMed] [Google Scholar]
  48. Rosenfeld P. J., O'Neill E. A., Wides R. J., Kelly T. J. Sequence-specific interactions between cellular DNA-binding proteins and the adenovirus origin of DNA replication. Mol Cell Biol. 1987 Feb;7(2):875–886. doi: 10.1128/mcb.7.2.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Santoro C., Mermod N., Andrews P. C., Tjian R. A family of human CCAAT-box-binding proteins active in transcription and DNA replication: cloning and expression of multiple cDNAs. Nature. 1988 Jul 21;334(6179):218–224. doi: 10.1038/334218a0. [DOI] [PubMed] [Google Scholar]
  50. Sasaguri Y., Sanford T., Aguirre P., Padmanabhan R. Immunological analysis of 140-kDa adenovirus-encoded DNA polymerase in adenovirus type 2-infected HeLa cells using antibodies raised against the protein expressed in Escherichia coli. Virology. 1987 Oct;160(2):389–399. doi: 10.1016/0042-6822(87)90010-9. [DOI] [PubMed] [Google Scholar]
  51. Schneider R., Gander I., Müller U., Mertz R., Winnacker E. L. A sensitive and rapid gel retention assay for nuclear factor I and other DNA-binding proteins in crude nuclear extracts. Nucleic Acids Res. 1986 Feb 11;14(3):1303–1317. doi: 10.1093/nar/14.3.1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Silver P. A. How proteins enter the nucleus. Cell. 1991 Feb 8;64(3):489–497. doi: 10.1016/0092-8674(91)90233-o. [DOI] [PubMed] [Google Scholar]
  53. Stillman B. W., Topp W. C., Engler J. A. Conserved sequences at the origin of adenovirus DNA replication. J Virol. 1982 Nov;44(2):530–537. doi: 10.1128/jvi.44.2.530-537.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Stillman B. Initiation of eukaryotic DNA replication in vitro. Annu Rev Cell Biol. 1989;5:197–245. doi: 10.1146/annurev.cb.05.110189.001213. [DOI] [PubMed] [Google Scholar]
  55. Stuiver M. H., van der Vliet P. C. Adenovirus DNA-binding protein forms a multimeric protein complex with double-stranded DNA and enhances binding of nuclear factor I. J Virol. 1990 Jan;64(1):379–386. doi: 10.1128/jvi.64.1.379-386.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Sturm R. A., Das G., Herr W. The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. Genes Dev. 1988 Dec;2(12A):1582–1599. doi: 10.1101/gad.2.12a.1582. [DOI] [PubMed] [Google Scholar]
  57. Sugawara K., Gilead Z., Wold W. S., Green M. Immunofluorescence study of the adenovirus type 2 single-stranded DNA binding protein in infected and transformed cells. J Virol. 1977 May;22(2):527–539. doi: 10.1128/jvi.22.2.527-539.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Tamanoi F., Stillman B. W. Initiation of adenovirus DNA replication in vitro requires a specific DNA sequence. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6446–6450. doi: 10.1073/pnas.80.21.6446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Temperley S. M., Burrow C. R., Kelly T. J., Hay R. T. Identification of two distinct regions within the adenovirus minimal origin of replication that are required for adenovirus type 4 DNA replication in vitro. J Virol. 1991 Sep;65(9):5037–5044. doi: 10.1128/jvi.65.9.5037-5044.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Temperley S. M., Hay R. T. Replication of adenovirus type 4 DNA by a purified fraction from infected cells. Nucleic Acids Res. 1991 Jun 25;19(12):3243–3249. doi: 10.1093/nar/19.12.3243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Verrijzer C. P., Kal A. J., Van der Vliet P. C. The DNA binding domain (POU domain) of transcription factor oct-1 suffices for stimulation of DNA replication. EMBO J. 1990 Jun;9(6):1883–1888. doi: 10.1002/j.1460-2075.1990.tb08314.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Voelkerding K., Klessig D. F. Identification of two nuclear subclasses of the adenovirus type 5-encoded DNA-binding protein. J Virol. 1986 Nov;60(2):353–362. doi: 10.1128/jvi.60.2.353-362.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Walton T. H., Moen P. T., Jr, Fox E., Bodnar J. W. Interactions of minute virus of mice and adenovirus with host nucleoli. J Virol. 1989 Sep;63(9):3651–3660. doi: 10.1128/jvi.63.9.3651-3660.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Whyte P., Buchkovich K. J., Horowitz J. M., Friend S. H., Raybuck M., Weinberg R. A., Harlow E. Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature. 1988 Jul 14;334(6178):124–129. doi: 10.1038/334124a0. [DOI] [PubMed] [Google Scholar]
  65. Wides R. J., Challberg M. D., Rawlins D. R., Kelly T. J. Adenovirus origin of DNA replication: sequence requirements for replication in vitro. Mol Cell Biol. 1987 Feb;7(2):864–874. doi: 10.1128/mcb.7.2.864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Wilcock D., Lane D. P. Localization of p53, retinoblastoma and host replication proteins at sites of viral replication in herpes-infected cells. Nature. 1991 Jan 31;349(6308):429–431. doi: 10.1038/349429a0. [DOI] [PubMed] [Google Scholar]
  67. Williams J. F. Enhancement of adenovirus plaque formation on HeLa cells by magnesium chloride. J Gen Virol. 1970 Dec;9(3):251–255. doi: 10.1099/0022-1317-9-3-251. [DOI] [PubMed] [Google Scholar]
  68. Yamamoto S., Takahashi T., Matsukage A. Tight association of DNA polymerase alpha with granular structures in the nuclear matrix of chick embryo cell: immunocytochemical detection with monoclonal antibody against DNA polymerase alpha. Cell Struct Funct. 1984 Mar;9(1):83–90. doi: 10.1247/csf.9.83. [DOI] [PubMed] [Google Scholar]
  69. de Vries E., van Driel W., Tromp M., van Boom J., van der Vliet P. C. Adenovirus DNA replication in vitro: site-directed mutagenesis of the nuclear factor I binding site of the Ad2 origin. Nucleic Acids Res. 1985 Jul 11;13(13):4935–4952. doi: 10.1093/nar/13.13.4935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. van Bergen B. G., van der Ley P. A., van Driel W., van Mansfeld A. D., van der Vliet P. C. Replication of origin containing adenovirus DNA fragments that do not carry the terminal protein. Nucleic Acids Res. 1983 Apr 11;11(7):1975–1989. doi: 10.1093/nar/11.7.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]

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