Origins of bidirectional replication of Epstein-Barr virus: Models for understanding mammalian origins of DNA synthesis

Abstract

Epstein-Barr virus (EBV), provides unique advantages to understand origins of replication in higher eukaryotes. EBV establishes itself efficiently in infected B lymphocytes, where it exists as a 165 kb, circular chromosome which is duplicated once per cell cycle (Adams [1987] J Virol 61:1743-1746). Five to twenty copies of the EBV chromosome are usually present in each cell, increasing the signal/noise ratio for mapping and analyzing its replication origins. Remarkably only one viral protein is required for the synthesis and partitioning of the viral chromosomes: EBV nuclear antigen-1, or EBNA1. EBV uses distinct origins related to the ARS1 origin of Saccharomyces cerevisiae and to that of the dihydrofolate reductase (DHFR) locus in Chinese hamster ovary (CHO) cells [Bogan et al., 2000]. We shall review the properties and the regulation of these two kinds of origins in EBV and relate them to their cellular cousins.

Non-integrating lentiviral vectors based on the minimal S/MAR sequence retain transgene expression in dividing cells

“…However, because these LTR circles lack an origin of replication (ori), they cannot self-propagate during cell division and are eventually lost in dividing cells (Apolonia et al, 2007;Butler et al, 2002;Pierson et al, 2002 (Vargas et al, 2008). The ori sequences from viral genomes do provide episomal persistence but also introduce safety problems, such as the potential risk of immunogenesis or transformation (Moens et al, 1997;Slinskey et al, 1999;Wang and Sugden, 2005). In mammalian genomes, there are types of DNA elements that interact with elements in the nuclear matrix to separate the chromosome into specific spatial domains and modulate temporal DNA replication and gene expression during cell cycles (Hagedorn et al, 2011;Mirkovitch et al, 1984).…”

Symmetrical localization of extrachromosomally replicating viral genomes on sister chromatids

“…Human replication complexes, such as origin recognition complex (ORC) and mini-chromosome maintenance (MCM) proteins, have been shown to reside in the oriP region of EBV plasmids Dhar et al, 2001;Schepers et al, 2001). Thus, it appears that EBV latent replication is mediated entirely by the cellular replication machinery (reviewed in Wang and Sugden, 2005), which also explains why EBV episomes replicate only once per host-cell cycle (Yates and Guan, 1991).…”

Sequence-Directed DNA Curvature in Replication Origins Segments

“…Prokaryotic cells are examples of organisms that display a fast and precise replication process (Robinson & Bell, 2005;Wang & Sugden, 2005). Although the consensus nucleotide sequence in the bacterial replication origin exhibits variation in number and size between different bacterial species (DoriC, a database of the oriC region in bacterial genomes; Gimenes et al, 2008a), it is capable of directing the association of specific proteins in the initiator chromosomal site and thereby the success of the replicative process in eubacteria (reviewed in Mott & Berger, 2007).…”