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The plasmid replicon of EBV consists of multiple cis-acting elements that facilitate DNA synthesis by the cell and a viral maintenance element.
EMBO J. 1998 Nov 02; 17(21):6394-403.EJ

Abstract

Plasmids containing oriP, the plasmid origin of Epstein-Barr virus (EBV), are replicated stably in human cells that express a single viral trans-acting factor, EBNA-1. Unlike plasmids of other viruses, but akin to human chromosomes, oriP plasmids are synthesized once per cell cycle, and are partitioned faithfully to daughter cells during mitosis. Although EBNA-1 binds multiple sites within oriP, its role in DNA synthesis and partitioning has been obscure. EBNA-1 lacks enzymatic activities that are present in the origin-binding proteins of other mammalian viruses, and does not interact with human cellular proteins that provide equivalent enzymatic functions. We demonstrate that plasmids with oriP or its constituent elements are synthesized efficiently in human cells in the absence of EBNA-1. Further, we show that human cells rapidly eliminate or destroy newly synthesized plasmids, and that both EBNA-1 and the family of repeats of oriP are required for oriP plasmids to escape this catastrophic loss. These findings indicate that EBV's plasmid replicon consists of genetic elements with distinct functions, multiple cis-acting elements that facilitate DNA synthesis and viral cis/trans elements that permit retention of replicated DNA in daughter cells. They also explain historical failures to identify mammalian origins of DNA synthesis as autonomously replicating sequences.

Authors+Show Affiliations

McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9799247

Citation

Aiyar, A, et al. "The Plasmid Replicon of EBV Consists of Multiple Cis-acting Elements That Facilitate DNA Synthesis By the Cell and a Viral Maintenance Element." The EMBO Journal, vol. 17, no. 21, 1998, pp. 6394-403.
Aiyar A, Tyree C, Sugden B. The plasmid replicon of EBV consists of multiple cis-acting elements that facilitate DNA synthesis by the cell and a viral maintenance element. EMBO J. 1998;17(21):6394-403.
Aiyar, A., Tyree, C., & Sugden, B. (1998). The plasmid replicon of EBV consists of multiple cis-acting elements that facilitate DNA synthesis by the cell and a viral maintenance element. The EMBO Journal, 17(21), 6394-403.
Aiyar A, Tyree C, Sugden B. The Plasmid Replicon of EBV Consists of Multiple Cis-acting Elements That Facilitate DNA Synthesis By the Cell and a Viral Maintenance Element. EMBO J. 1998 Nov 2;17(21):6394-403. PubMed PMID: 9799247.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The plasmid replicon of EBV consists of multiple cis-acting elements that facilitate DNA synthesis by the cell and a viral maintenance element. AU - Aiyar,A, AU - Tyree,C, AU - Sugden,B, PY - 1998/11/3/pubmed PY - 1998/11/3/medline PY - 1998/11/3/entrez SP - 6394 EP - 403 JF - The EMBO journal JO - EMBO J VL - 17 IS - 21 N2 - Plasmids containing oriP, the plasmid origin of Epstein-Barr virus (EBV), are replicated stably in human cells that express a single viral trans-acting factor, EBNA-1. Unlike plasmids of other viruses, but akin to human chromosomes, oriP plasmids are synthesized once per cell cycle, and are partitioned faithfully to daughter cells during mitosis. Although EBNA-1 binds multiple sites within oriP, its role in DNA synthesis and partitioning has been obscure. EBNA-1 lacks enzymatic activities that are present in the origin-binding proteins of other mammalian viruses, and does not interact with human cellular proteins that provide equivalent enzymatic functions. We demonstrate that plasmids with oriP or its constituent elements are synthesized efficiently in human cells in the absence of EBNA-1. Further, we show that human cells rapidly eliminate or destroy newly synthesized plasmids, and that both EBNA-1 and the family of repeats of oriP are required for oriP plasmids to escape this catastrophic loss. These findings indicate that EBV's plasmid replicon consists of genetic elements with distinct functions, multiple cis-acting elements that facilitate DNA synthesis and viral cis/trans elements that permit retention of replicated DNA in daughter cells. They also explain historical failures to identify mammalian origins of DNA synthesis as autonomously replicating sequences. SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/9799247/The_plasmid_replicon_of_EBV_consists_of_multiple_cis_acting_elements_that_facilitate_DNA_synthesis_by_the_cell_and_a_viral_maintenance_element_ L2 - https://doi.org/10.1093/emboj/17.21.6394 DB - PRIME DP - Unbound Medicine ER -