DOI: 10.1242/jcs.00708. Complex protein-DNA dynamics at the latent origin of DNA replication of Epstein-Barr virus

Complex protein-DNA dynamics at the latent origin of DNA replication of Epstein-Barr virus
10.1242/jcs.00708
Crossref journal-article
The Company of Biologists
Journal of Cell Science (237)
Abstract
The sequential binding of the origin recognition complex (ORC), Cdc6p and the minichromosome maintenance proteins (MCM2-7) mediates replication competence at eukaryotic origins of DNA replication. The latent origin of Epstein-Barr virus, oriP, is a viral origin known to recruit ORC. OriP also binds EBNA1, a virally encoded protein that lacks any activity predicted to be required for replication initiation. Here, we used chromatin immunoprecipitation and chromatin binding to compare the cell-cycle-dependent binding of pre-RC components and EBNA1 to oriP and to global cellular chromatin. Prereplicative-complex components such as the Mcm2p-Mcm7p proteins and HsOrc1p are regulated in a cell-cycle-dependent fashion, whereas other HsOrc subunits and EBNA1 remain constantly bound. In addition, HsOrc1p becomes sensitive to the 26S proteasome after release from DNA during S phase. These results show that the complex protein-DNA dynamics at the viral oriP are synchronized with the cell division cycle. Chromatin-binding and chromatin-immunoprecipitation experiments on G0 arrested cells indicated that the ORC core complex (ORC2-5) and EBNA1 remain bound to chromatin and oriP. HsOrc6p and the MCM2-7 complex are released in resting cells. HsOrc1p is partly liberated from chromatin. Our data suggest that origins remain marked in resting cells by the ORC core complex to ensure a rapid and regulated reentry into the cell cycle. These findings indicate that HsOrc is a dynamic complex and that its DNA binding activity is regulated differently in the various stages of the cell cycle.
Bibliography
Ritzi, M., Tillack, K., Gerhardt, J., Ott, E., Humme, S., Kremmer, E., Hammerschmidt, W., & Schepers, A. (2003). Complex protein-DNA dynamics at the latent origin of DNA replication of Epstein-Barr virus. Journal of Cell Science, 116(19), 3971â3984.
Authors 8
Marion Ritzi (first)
Kristina Tillack (additional)
Jeannine Gerhardt (additional)
Elisabeth Ott (additional)
Sibille Humme (additional)
Elisabeth Kremmer (additional)
Wolfgang Hammerschmidt (additional)
Aloys Schepers (additional)
References 74 Referenced 91
Dates
Type	When
Created	21 years, 11 months ago (Sept. 2, 2003, 2:42 p.m.)
Deposited	2 years, 4 months ago (April 26, 2023, 5:11 p.m.)
Indexed	3 months ago (May 21, 2025, 12:05 p.m.)
Issued	21 years, 10 months ago (Oct. 1, 2003)
Published	21 years, 10 months ago (Oct. 1, 2003)
Published Print	21 years, 10 months ago (Oct. 1, 2003)
Funders 0
None
BibTeX
@article{Ritzi_2003, title={Complex protein-DNA dynamics at the latent origin of DNA replication of Epstein-Barr virus}, volume={116}, ISSN={0021-9533}, url={http://dx.doi.org/10.1242/jcs.00708}, DOI={10.1242/jcs.00708}, number={19}, journal={Journal of Cell Science}, publisher={The Company of Biologists}, author={Ritzi, Marion and Tillack, Kristina and Gerhardt, Jeannine and Ott, Elisabeth and Humme, Sibille and Kremmer, Elisabeth and Hammerschmidt, Wolfgang and Schepers, Aloys}, year={2003}, month=oct, pages={3971–3984} }
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  "abstract": "<jats:p>The sequential binding of the origin recognition complex (ORC), Cdc6p and the minichromosome maintenance proteins (MCM2-7) mediates replication competence at eukaryotic origins of DNA replication. The latent origin of Epstein-Barr virus, oriP, is a viral origin known to recruit ORC. OriP also binds EBNA1, a virally encoded protein that lacks any activity predicted to be required for replication initiation. Here, we used chromatin immunoprecipitation and chromatin binding to compare the cell-cycle-dependent binding of pre-RC components and EBNA1 to oriP and to global cellular chromatin. Prereplicative-complex components such as the Mcm2p-Mcm7p proteins and HsOrc1p are regulated in a cell-cycle-dependent fashion, whereas other HsOrc subunits and EBNA1 remain constantly bound. In addition, HsOrc1p becomes sensitive to the 26S proteasome after release from DNA during S phase. These results show that the complex protein-DNA dynamics at the viral oriP are synchronized with the cell division cycle. Chromatin-binding and chromatin-immunoprecipitation experiments on G0 arrested cells indicated that the ORC core complex (ORC2-5) and EBNA1 remain bound to chromatin and oriP. HsOrc6p and the MCM2-7 complex are released in resting cells. HsOrc1p is partly liberated from chromatin. Our data suggest that origins remain marked in resting cells by the ORC core complex to ensure a rapid and regulated reentry into the cell cycle. These findings indicate that HsOrc is a dynamic complex and that its DNA binding activity is regulated differently in the various stages of the cell cycle.</jats:p>",
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