This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wonderling, R. S.
Right arrow Articles by Owens, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wonderling, R. S.
Right arrow Articles by Owens, R. A.

 Previous Article  |  Next Article 

J. Virol., Mar 1997, 2528-2534, Vol 71, No. 3
Copyright © 1997, American Society for Microbiology

Binding sites for adeno-associated virus Rep proteins within the human genome

RS Wonderling and RA Owens
Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.

The Rep proteins of adeno-associated virus type 2 (AAV) are known to bind to Rep recognition sequences (RRSs) in the AAV inverted terminal repeats (ITRs), the AAV p5 promoter, and the preferred AAV integration site in human chromosome 19, called AAVS1. Integration of the AAV genome into AAVS1 appears to be mediated by an interaction between the Rep proteins of AAV and Rep binding sites within the viral genome and the integration locus. In an attempt to identify potential alternate integration sites, we looked for recognition sites for AAV Rep proteins in the human genome by performing a BLASTN computerized homology search. We used the 16-mer core sequences of the RRSs in the AAV ITRs and AAVS1 separately as query sequences and identified 18 new RRSs in or flanking the genes coding for the following: tyrosine kinase activator protein 1 (TKA-1); colony stimulating factor-1; insulin-like growth factor binding protein 2 (IGFBP-2); histone H2B.1; basement membrane heparan sulfate proteoglycan, also known as perlecan; the AF-9 gene product, which is involved in the chromosomal translocation t (9:11)(p22:q23); the betaB subunit of the hormone known as inhibin; interleukin-2 enhancer binding factor; an endoplasmic reticulum-Golgi intermediate compartment resident protein called p63; a global transcription activator (hSNF2L); the beta-actin repair domain; a retinoic acid-inducible factor, also known as midkine; a breast tumor autoantigen; a growth-arrest- and DNA-damage-inducible protein called gadd45; the cyclin-dependent kinase inhibitor called KIP2, which inhibits several G1 cyclin-cyclin-dependent kinase complexes; and the hereditary breast and ovarian cancer gene (BRCA1). RRSs were also identified in a newly discovered open reading frame on chromosome 10 and in the ERCC1 locus on human chromosome 19. The ability of a maltose binding protein-Rep68 fusion protein to bind to these sequences was confirmed by electrophoretic mobility shift assays. These sites may serve as alternate integration sites for AAV or play a role in Rep- mediated effects on human cells.


This article has been cited by other articles:

  • Dutheil, N., Henckaerts, E., Kohlbrenner, E., Linden, R. M. (2009). Transcriptional Analysis of the Adeno-Associated Virus Integration Site. J. Virol. 83: 12512-12525 [Abstract] [Full Text]  
  • Needham, P. G., Casper, J. M., Kalman-Maltese, V., Verrill, K., Dignam, J. D., Trempe, J. P. (2006). Adeno-associated virus rep protein-mediated inhibition of transcription of the adenovirus major late promoter in vitro.. J. Virol. 80: 6207-6217 [Abstract] [Full Text]  
  • Jang, M. Y., Yarborough, O. H. III, Conyers, G. B., McPhie, P., Owens, R. A. (2005). Stable Secondary Structure near the Nicking Site for Adeno-Associated Virus Type 2 Rep Proteins on Human Chromosome 19. J. Virol. 79: 3544-3556 [Abstract] [Full Text]  
  • Casper, J. M., Timpe, J. M., Dignam, J. D., Trempe, J. P. (2005). Identification of an Adeno-Associated Virus Rep Protein Binding Site in the Adenovirus E2a Promoter. J. Virol. 79: 28-38 [Abstract] [Full Text]  
  • Amiss, T. J., McCarty, D. M., Skulimowski, A., Samulski, R. J. (2003). Identification and Characterization of an Adeno-Associated Virus Integration Site in CV-1 Cells from the African Green Monkey. J. Virol. 77: 1904-1915 [Abstract] [Full Text]  
  • Cathomen, T., Stracker, T. H., Gilbert, L. B., Weitzman, M. D. (2001). A genetic screen identifies a cellular regulator of adeno-associated virus. Proc. Natl. Acad. Sci. USA 10.1073/pnas.261567198v1 [Abstract] [Full Text]  
  • Lamartina, S., Ciliberto, G., Toniatti, C. (2000). Selective Cleavage of AAVS1 Substrates by the Adeno-Associated Virus Type 2 Rep68 Protein Is Dependent on Topological and Sequence Constraints. J. Virol. 74: 8831-8842 [Abstract] [Full Text]  
  • Brister, J. R., Muzyczka, N. (2000). Mechanism of Rep-Mediated Adeno-Associated Virus Origin Nicking. J. Virol. 74: 7762-7771 [Abstract] [Full Text]  
  • Meneses, P., Berns, K. I., Winocour, E. (2000). DNA Sequence Motifs Which Direct Adeno-Associated Virus Site-Specific Integration in a Model System. J. Virol. 74: 6213-6216 [Abstract] [Full Text]  
  • Young, S. M. Jr., McCarty, D. M., Degtyareva, N., Samulski, R. J. (2000). Roles of Adeno-Associated Virus Rep Protein and Human Chromosome 19 in Site-Specific Recombination. J. Virol. 74: 3953-3966 [Abstract] [Full Text]  
  • Davis, M. D., Wu, J., Owens, R. A. (2000). Mutational Analysis of Adeno-Associated Virus Type 2 Rep68 Protein Endonuclease Activity on Partially Single-Stranded Substrates. J. Virol. 74: 2936-2942 [Abstract] [Full Text]  
  • Cathomen, T., Collete, D., Weitzman, M. D. (2000). A Chimeric Protein Containing the N Terminus of the Adeno-Associated Virus Rep Protein Recognizes Its Target Site in an In Vivo Assay. J. Virol. 74: 2372-2382 [Abstract] [Full Text]  
  • Zhan, D., Santin, A. D., Liu, Y., Parham, G. P., Li, C., Meyers, C., Hermonat, P. L. (1999). Binding of the Human Papillomavirus Type 16 p97 Promoter by the Adeno-associated Virus Rep78 Major Regulatory Protein Correlates with Inhibition. J. Biol. Chem. 274: 31619-31624 [Abstract] [Full Text]  
  • Wu, J., Davis, M. D., Owens, R. A. (1999). Factors Affecting the Terminal Resolution Site Endonuclease, Helicase, and ATPase Activities of Adeno-Associated Virus Type 2 Rep Proteins. J. Virol. 73: 8235-8244 [Abstract] [Full Text]  
  • Chiorini, J. A., Afione, S., Kotin, R. M. (1999). Adeno-Associated Virus (AAV) Type 5 Rep Protein Cleaves a Unique Terminal Resolution Site Compared with Other AAV Serotypes. J. Virol. 73: 4293-4298 [Abstract] [Full Text]  
  • Chatterjee, S., Li, W., Wong, C. A., Fisher-Adams, G., Lu, D., Guha, M., Macer, J. A., Forman, S. J., Wong, K.K. Jr (1999). Transduction of Primitive Human Marrow and Cord Blood-Derived Hematopoietic Progenitor Cells With Adeno-Associated Virus Vectors. Blood 93: 1882-1894 [Abstract] [Full Text]  
  • Davis, M. D., Wonderling, R. S., Walker, S. L., Owens, R. A. (1999). Analysis of the Effects of Charge Cluster Mutations in Adeno-Associated Virus Rep68 Protein In Vitro. J. Virol. 73: 2084-2093 [Abstract] [Full Text]  
  • Cathomen, T., Stracker, T. H., Gilbert, L. B., Weitzman, M. D. (2001). A genetic screen identifies a cellular regulator of adeno-associated virus. Proc. Natl. Acad. Sci. USA 98: 14991-14996 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»