J. Biochem, 1998, Vol. 123, No. 1 175-181
© 1998 Japanese Biochemical Society
research-article |
Identification of Minimal oriP of Epstein-Barr Virus Required for DNA Replication1
Department of Cell Regulation, Division of Virology and Immunology, Medical Research Institute, Tokyo Medical and Dental University Yushima 1-5-45, Bunkyo-ku, Tokyo 113
2To whom correspondence should be addressed. E-mail: hirai.creg{at}mri.tmd.ac.jp
DNA replication from oriP of Epstein-Barr virus is mediated by the virus replication factor EBNA1 and cellular factors and occurs approximately once in each cell cycle. We have identified a minimal oriP element that is necessary and sufficient for DNA replication. We transfected plasmids containing several oriP fragments into HeLa cells expressing EBNA1 and analyzed their replication during four days after transfection using the methylation sensitive restriction endonuclease DpnI. All the oriP fragments containing the four EBNA1-binding sites known as the dyad symmetry sequence (DS) initiated DNA replication. The sequences flanking DS were not essential for DNA replication, but deletion of two or three EBNA1-binding sites in DS significantly reduced or totally abolished its replication activity. These results indicated that the four EBNA1-binding sites in DS constitute the minimal oriP element for DNA replication and suggest that DNA replication is initiated by recruitment of cellular replication factors onto or near the minimal oriP by EBNA1. We also found that the minimal oriP initiated DNA replication in mouse fibroblasts expressing EBNA1 but worked only at reduced efficiency, suggesting species specificity in DNA replication machineries.
1This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan and by The Japan Health Sciences Foundation.
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