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Initiation of latent DNA replication in the Epstein-Barr virus genome can occur at sites other than the genetically defined origin.
Mol Cell Biol. 1995 May; 15(5):2893-903.MC

Abstract

Our laboratory has previously shown that replication of a small plasmid, p174, containing the genetically defined Epstein-Barr virus (EBV) latent origin of replication, oriP, initiates within oriP at or near a dyad symmetry (DS) element and terminates specifically at a family of repeated sequences (FR), also located within oriP. We describe here an analysis of the replication of intact approximately 170-kb EBV genomes in four latently infected cell lines that uses two-dimensional gel replicon mapping. Initiation was detected at oriP in all EBV genomes examined; however, some replication forks appear to originate from alternative initiation sites. In addition, pausing of replication forks was observed at the two clusters of EBV nuclear antigen 1 binding sites within oriP and at or near two highly expressed viral genes 0.5 to 1 kb upstream of oriP, the EBV-encoded RNA (EBER) genes. In the Raji EBV genome, the relative abundance of these stalled forks and the direction in which they are stalled indicate that most replication forks originate upstream of oriP. We thus searched for additional initiation sites in the Raji EBV and found that the majority of initiation events were distributed over a broad region to the left of oriP. This delocalized pattern of initiation resembles initiation of replication in several well-characterized mammalian chromosomal loci and is the first described for any viral genome. EBV thus provides a unique model system with which to investigate factors influencing the selection of replication initiation and termination sites in mammalian cells.

Authors+Show Affiliations

Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.No 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

7739569

Citation

Little, R D., and C L. Schildkraut. "Initiation of Latent DNA Replication in the Epstein-Barr Virus Genome Can Occur at Sites Other Than the Genetically Defined Origin." Molecular and Cellular Biology, vol. 15, no. 5, 1995, pp. 2893-903.
Little RD, Schildkraut CL. Initiation of latent DNA replication in the Epstein-Barr virus genome can occur at sites other than the genetically defined origin. Mol Cell Biol. 1995;15(5):2893-903.
Little, R. D., & Schildkraut, C. L. (1995). Initiation of latent DNA replication in the Epstein-Barr virus genome can occur at sites other than the genetically defined origin. Molecular and Cellular Biology, 15(5), 2893-903.
Little RD, Schildkraut CL. Initiation of Latent DNA Replication in the Epstein-Barr Virus Genome Can Occur at Sites Other Than the Genetically Defined Origin. Mol Cell Biol. 1995;15(5):2893-903. PubMed PMID: 7739569.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Initiation of latent DNA replication in the Epstein-Barr virus genome can occur at sites other than the genetically defined origin. AU - Little,R D, AU - Schildkraut,C L, PY - 1995/5/1/pubmed PY - 1995/5/1/medline PY - 1995/5/1/entrez SP - 2893 EP - 903 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 15 IS - 5 N2 - Our laboratory has previously shown that replication of a small plasmid, p174, containing the genetically defined Epstein-Barr virus (EBV) latent origin of replication, oriP, initiates within oriP at or near a dyad symmetry (DS) element and terminates specifically at a family of repeated sequences (FR), also located within oriP. We describe here an analysis of the replication of intact approximately 170-kb EBV genomes in four latently infected cell lines that uses two-dimensional gel replicon mapping. Initiation was detected at oriP in all EBV genomes examined; however, some replication forks appear to originate from alternative initiation sites. In addition, pausing of replication forks was observed at the two clusters of EBV nuclear antigen 1 binding sites within oriP and at or near two highly expressed viral genes 0.5 to 1 kb upstream of oriP, the EBV-encoded RNA (EBER) genes. In the Raji EBV genome, the relative abundance of these stalled forks and the direction in which they are stalled indicate that most replication forks originate upstream of oriP. We thus searched for additional initiation sites in the Raji EBV and found that the majority of initiation events were distributed over a broad region to the left of oriP. This delocalized pattern of initiation resembles initiation of replication in several well-characterized mammalian chromosomal loci and is the first described for any viral genome. EBV thus provides a unique model system with which to investigate factors influencing the selection of replication initiation and termination sites in mammalian cells. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/7739569/Initiation_of_latent_DNA_replication_in_the_Epstein_Barr_virus_genome_can_occur_at_sites_other_than_the_genetically_defined_origin_ L2 - https://journals.asm.org/doi/10.1128/MCB.15.5.2893?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -