Nucleic Acids Research, 2001, Vol. 29, No. 17 3520-3528
© 2001 Oxford University Press
Epstein–Barr nuclear antigen 1 binds and destabilizes nucleosomes at the viral origin of latent DNA replication
Department of Medical Genetics and Microbiology and 1Department of Biochemistry, University of Toronto, 1 Kings College Circle, Toronto, Ontario M5S 1A8, Canada
The EBNA1 protein of Epstein–Barr virus (EBV) activates latent-phase DNA replication by an unknown mechanism that involves binding to four recognition sites in the dyad symmetry (DS) element of the viral latent origin of DNA replication. Since EBV episomes are assembled into nucleosomes, we have examined the ability of Epstein–Barr virus nuclear antigen 1 (EBNA1) to interact with the DS element when it is assembled into a nucleosome core particle. EBNA1 bound to its recognition sites within this nucleosome, forming a ternary complex, and displaced the histone octamer upon competitor DNA challenge. The DNA binding and dimerization region of EBNA1 was sufficient for nucleosome binding and destabilization. Although EBNA1 was able to bind to nucleosomes containing two recognition sites from the DS element positioned at the edge of the nucleosome, nucleosome destabilization was only observed when all four sites of the DS element were present. Our results indicate that the presence of a nucleosome at the viral origin will not prevent EBNA1 binding to its recognition sites. In addition, since four EBNA1 recognition sites are required for both nucleosome destabilization and efficient origin activation, our findings also suggest that nucleosome destabilization by EBNA1 is important for origin activation.
* To whom correspondence should be addressed. Tel: +1 416 946 3501; Fax: +1 416 978 6885; Email: lori.frappier{at}utoronto.ca
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. K. Nayyar, K. Shire, and L. Frappier Mitotic chromosome interactions of Epstein-Barr nuclear antigen 1 (EBNA1) and human EBNA1-binding protein 2 (EBP2) J. Cell Sci., December 1, 2009; 122(23): 4341 - 4350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wang and L. Frappier Nucleosome Assembly Proteins Bind to Epstein-Barr Virus Nuclear Antigen 1 and Affect Its Functions in DNA Replication and Transcriptional Activation J. Virol., November 15, 2009; 83(22): 11704 - 11714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Workman Nucleosome displacement in transcription Genes & Dev., August 1, 2006; 20(15): 2009 - 2017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sears, J. Kolman, G. M. Wahl, and A. Aiyar Metaphase Chromosome Tethering Is Necessary for the DNA Synthesis and Maintenance of oriP Plasmids but Is Insufficient for Transcription Activation by Epstein-Barr Nuclear Antigen 1 J. Virol., November 1, 2003; 77(21): 11767 - 11780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kennedy and B. Sugden EBNA-1, a Bifunctional Transcriptional Activator Mol. Cell. Biol., October 1, 2003; 23(19): 6901 - 6908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Okuley, M. Call, T. Mitchell, B. Hu, and M. E. Woodworth Relationship among Location of T-Antigen-Induced DNA Distortion, Auxiliary Sequences, and DNA Replication Efficiency J. Virol., October 1, 2003; 77(19): 10651 - 10657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wu, P. Kapoor, and L. Frappier Separation of the DNA Replication, Segregation, and Transcriptional Activation Functions of Epstein-Barr Nuclear Antigen 1 J. Virol., March 1, 2002; 76(5): 2480 - 2490. [Abstract] [Full Text] [PDF]
|
|