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. 1994 Oct;68(10):6799–6803. doi: 10.1128/jvi.68.10.6799-6803.1994

Human herpesvirus 6B origin: sequence diversity, requirement for two binding sites for origin-binding protein, and enhanced replication from origin multimers.

S Dewhurst 1, D M Krenitsky 1, C Dykes 1
PMCID: PMC237107  PMID: 8084018

Abstract

A previously identified human herpesvirus 6B (HHV-6B) origin of DNA replication contains two binding sites for the origin-binding protein (OBPH6B). We have investigated the functional significance of these sites by determining the replication efficiencies of mutated origin sequences, using a transient replication assay. The results indicate that both sites are required for DNA replication. In addition, we have tested the functional consequences of linear sequence amplifications in the origin. The data show that tandemized origin elements are more efficiently replicated than single-copy origins. Finally, we have determined the extent of interstrain origin sequence variation that exists among HHV-6 isolates by cloning, sequencing, and analyzing origins from a number of virus isolates, including examples of both HHV-6A and HHV-6B.

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Selected References

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

  1. Dabrowski C. E., Carmillo P. J., Schaffer P. A. Cellular protein interactions with herpes simplex virus type 1 oriS. Mol Cell Biol. 1994 Apr;14(4):2545–2555. doi: 10.1128/mcb.14.4.2545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dewhurst S., Dollard S. C., Pellett P. E., Dambaugh T. R. Identification of a lytic-phase origin of DNA replication in human herpesvirus 6B strain Z29. J Virol. 1993 Dec;67(12):7680–7683. doi: 10.1128/jvi.67.12.7680-7683.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Elias P., Gustafsson C. M., Hammarsten O. The origin binding protein of herpes simplex virus 1 binds cooperatively to the viral origin of replication oris. J Biol Chem. 1990 Oct 5;265(28):17167–17173. [PubMed] [Google Scholar]
  5. Graham G. J., Maio J. J. A rapid and reliable method to create tandem arrays of short DNA sequences. Biotechniques. 1992 Nov;13(5):780–789. [PubMed] [Google Scholar]
  6. Gustafsson C. M., Hammarsten O., Falkenberg M., Elias P. Herpes simplex virus DNA replication: a spacer sequence directs the ATP-dependent formation of a nucleoprotein complex at oriS. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4629–4633. doi: 10.1073/pnas.91.11.4629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hernandez T. R., Dutch R. E., Lehman I. R., Gustafsson C., Elias P. Mutations in a herpes simplex virus type 1 origin that inhibit interaction with origin-binding protein also inhibit DNA replication. J Virol. 1991 Mar;65(3):1649–1652. doi: 10.1128/jvi.65.3.1649-1652.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Higuchi R., Krummel B., Saiki R. K. A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. Nucleic Acids Res. 1988 Aug 11;16(15):7351–7367. doi: 10.1093/nar/16.15.7351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Human herpesvirus-6 strain groups: a nomenclature. Arch Virol. 1993;129(1-4):363–366. doi: 10.1007/BF01316913. [DOI] [PubMed] [Google Scholar]
  10. Inoue N., Dambaugh T. R., Rapp J. C., Pellett P. E. Alphaherpesvirus origin-binding protein homolog encoded by human herpesvirus 6B, a betaherpesvirus, binds to nucleotide sequences that are similar to ori regions of alphaherpesviruses. J Virol. 1994 Jul;68(7):4126–4136. doi: 10.1128/jvi.68.7.4126-4136.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Karlin S., Mocarski E. S., Schachtel G. A. Molecular evolution of herpesviruses: genomic and protein sequence comparisons. J Virol. 1994 Mar;68(3):1886–1902. doi: 10.1128/jvi.68.3.1886-1902.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koff A., Schwedes J. F., Tegtmeyer P. Herpes simplex virus origin-binding protein (UL9) loops and distorts the viral replication origin. J Virol. 1991 Jun;65(6):3284–3292. doi: 10.1128/jvi.65.6.3284-3292.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lockshon D., Galloway D. A. Sequence and structural requirements of a herpes simplex viral DNA replication origin. Mol Cell Biol. 1988 Oct;8(10):4018–4027. doi: 10.1128/mcb.8.10.4018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lusso P., Gallo R. C. Human herpesvirus 6 in AIDS. Lancet. 1994 Mar 5;343(8897):555–556. doi: 10.1016/s0140-6736(94)91515-6. [DOI] [PubMed] [Google Scholar]
  15. Martin D. W., Deb S. P., Klauer J. S., Deb S. Analysis of the herpes simplex virus type 1 OriS sequence: mapping of functional domains. J Virol. 1991 Aug;65(8):4359–4369. doi: 10.1128/jvi.65.8.4359-4369.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Natale D. A., Schubert A. E., Kowalski D. DNA helical stability accounts for mutational defects in a yeast replication origin. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2654–2658. doi: 10.1073/pnas.89.7.2654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Needleman S. B., Wunsch C. D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970 Mar;48(3):443–453. doi: 10.1016/0022-2836(70)90057-4. [DOI] [PubMed] [Google Scholar]
  18. Weir H. M., Stow N. D. Two binding sites for the herpes simplex virus type 1 UL9 protein are required for efficient activity of the oriS replication origin. J Gen Virol. 1990 Jun;71(Pt 6):1379–1385. doi: 10.1099/0022-1317-71-6-1379. [DOI] [PubMed] [Google Scholar]

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