Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by Geminin

Suman K. Dhar, Kenichi Yoshida, Yuichi Machida, Poonam Khaira, Biswendu Chaudhuri, James A. Wohlschlegel, Michael Leffak, John Yates, Anindya Dutta

Research output: Contribution to journalArticlepeer-review

243 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)287-296
Number of pages10
JournalCell
Volume106
Issue number3
DOIs
StatePublished - Aug 10 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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