TY - JOUR
T1 - Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by Geminin
AU - Dhar, Suman K.
AU - Yoshida, Kenichi
AU - Machida, Yuichi
AU - Khaira, Poonam
AU - Chaudhuri, Biswendu
AU - Wohlschlegel, James A.
AU - Leffak, Michael
AU - Yates, John
AU - Dutta, Anindya
N1 - Funding Information:
We thank members of the Dutta lab for discussions and C. Vaziri for Adeno-GFP. K.Y. created the Orc2 Δ/− HCT116 cell-line; S.K.D., K.Y., and Y.M. did the biochemistry; B.C. produced the data in Figure 6A and P.K. the data in Figure 4 . This work was supported by grants CA60499 (to A.D.), CA43122 (to J.Y.), and GM53819, and grants from the Kettering Foundation/WSU School of Medicine, the WSU CoSM (to M.L.), and a fellowship from the U.S. Army Breast Cancer Research program (to S.K.D.).
PY - 2001/8/10
Y1 - 2001/8/10
N2 - 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 β-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.
AB - 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 β-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.
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U2 - 10.1016/S0092-8674(01)00458-5
DO - 10.1016/S0092-8674(01)00458-5
M3 - Article
C2 - 11509178
AN - SCOPUS:0035839098
VL - 106
SP - 287
EP - 296
JO - Cell
JF - Cell
SN - 0092-8674
IS - 3
ER -