Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin.
A hypomorphic mutation made in the ORC2 gene of a human cancer cell line through homologous recombination decreased Orc2 protein levels by 90%. The G1 phase of the cell cycle was prolonged, but there was no effect on the utilization of either the c-Myc or beta-globin cellular origins of replication. Cells carrying this mutation failed to support the replication of a plasmid bearing the oriP replicator of Epstein Barr virus (EBV), and this defect was rescued by reintroduction of Orc2. Orc2 specifically associates with oriP in cells, most likely through its interaction with EBNA1. Geminin, an inhibitor of the mammalian replication initiation complex, inhibits replication from oriP. Therefore, ORC and the human replication initiation apparatus is required for replication from a viral origin of replication.
Dhar
S K
SK
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Yoshida
K
K
Machida
Y
Y
Khaira
P
P
Chaudhuri
B
B
Wohlschlegel
J A
JA
Leffak
M
M
Yates
J
J
Dutta
A
A
D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D016193:G1 Phase; D064248:Geminin; D016259:Genes, myc / Q000235:genetics; D005914:Globins / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D051738:Origin Recognition Complex; D010957:Plasmids / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D021122:Protein Subunits; D018741:Replication Origin / Q000235:genetics*; D014407:Tumor Cells, Cultured; D017735:Virus Latency / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; C577995:GMNN protein, human; D064248:Geminin; C497224:ORC2 protein, human; D051738:Origin Recognition Complex; D021122:Protein Subunits; D005914:Globins; C417029:EBV-encoded nuclear antigen 1