PMID- 17405814 OWN - NLM STAT- MEDLINE DCOM- 20071002 LR - 20211203 IS - 0021-9533 (Print) IS - 0021-9533 (Linking) VI - 120 IP - Pt 9 DP - 2007 May 1 TI - Symmetrical localization of extrachromosomally replicating viral genomes on sister chromatids. PG - 1529-39 AB - In eukaryotes, many latent viruses replicate as extrachromosomal molecules, called episomes, and efficiently segregate to daughter cells by noncovalently attaching to mitotic chromosomes. To understand the mechanism governing the processes, we analyzed the detailed subcellular localization of Epstein-Barr virus (EBV) genomes and a viral protein EBNA1, a bridging molecule between viral genomes and cellular chromatin. In the cells that were infected with a recombinant EBV expressing epitope-tagged EBNA1, EBNA1 localized to intranuclear punctate dots, which coincided with the localization of EBV genomes as revealed by fluorescence in situ hybridization (FISH). A significant number of EBNA1 dots were found to localize symmetrically on sister chromatids of mitotic chromosomes. Such symmetrical localization of EBNA1 dots was observed in prematurely condensed G2 chromosomes as well, correlating with the presence of closely spaced double dots of EBNA1 in G2-phase-enriched cells. The EBNA1 double dots were occasionally interconnected by the FISH signals of EBV episomes, exhibiting a dumbbell-like appearance. Thus, we propose that the partitioning of EBNA1 molecules onto sister chromatids during cellular DNA replication underlies the non-stochastic segregation of extrachromosomally replicating viral genomes. FAU - Kanda, Teru AU - Kanda T AD - Center for Virus Vector Development, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan. tkanda@igm.hokudai.ac.jp FAU - Kamiya, Masato AU - Kamiya M FAU - Maruo, Seiji AU - Maruo S FAU - Iwakiri, Dai AU - Iwakiri D FAU - Takada, Kenzo AU - Takada K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070403 PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (Chromosomal Proteins, Non-Histone) RN - 0 (Diketopiperazines) RN - 0 (Enzyme Inhibitors) RN - 0 (Epstein-Barr Virus Nuclear Antigens) RN - 0 (Marine Toxins) RN - 0 (Oxazoles) RN - 0 (Piperazines) RN - 0 (Topoisomerase II Inhibitors) RN - 0 (centromere protein C) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 21416-68-2 (4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione) RN - 7D07U14TK3 (calyculin A) RN - O5GA75RST7 (EBV-encoded nuclear antigen 1) RN - X6Q56QN5QC (Hydroxyurea) SB - IM MH - Cell Line, Tumor MH - Cell Nucleus/chemistry/genetics MH - Chromatids/*genetics MH - Chromosomal Proteins, Non-Histone/analysis/genetics/metabolism MH - DNA Replication/*genetics MH - Diketopiperazines MH - Enzyme Inhibitors/pharmacology MH - Epstein-Barr Virus Nuclear Antigens/analysis/genetics/metabolism MH - G2 Phase/genetics MH - Gene Dosage MH - *Genome, Viral MH - Green Fluorescent Proteins/genetics/metabolism MH - Herpesvirus 4, Human/*genetics MH - Humans MH - Hydroxyurea/pharmacology MH - In Situ Hybridization, Fluorescence MH - Marine Toxins MH - Mitosis/drug effects MH - Models, Genetic MH - Oxazoles/pharmacology MH - Piperazines/pharmacology MH - Plasmids/analysis/*genetics MH - Topoisomerase II Inhibitors EDAT- 2007/04/05 09:00 MHDA- 2007/10/03 09:00 CRDT- 2007/04/05 09:00 PHST- 2007/04/05 09:00 [pubmed] PHST- 2007/10/03 09:00 [medline] PHST- 2007/04/05 09:00 [entrez] AID - jcs.03434 [pii] AID - 10.1242/jcs.03434 [doi] PST - ppublish SO - J Cell Sci. 2007 May 1;120(Pt 9):1529-39. doi: 10.1242/jcs.03434. Epub 2007 Apr 3.