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Originally published In Press as doi:10.1074/jbc.M202163200 on April 4, 2002

J. Biol. Chem., Vol. 277, Issue 25, 22297-22303, June 21, 2002
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A Functional Interaction between the Human Papillomavirus 16 Transcription/Replication Factor E2 and the DNA Damage Response Protein TopBP1*

Winifred BonerDagger §, Ewan R. TaylorDagger , Emmanouella TsirimonakiDagger , Kazuhiko Yamane||**, M. Saveria CampoDagger , and Iain M. MorganDagger Dagger Dagger

From the Dagger  Institute of Comparative Medicine, Department of Veterinary Pathology, University of Glasgow, Garscube Estate, Bearsden Road, Glasgow G61 1QH, Scotland, the § Beatson Institute for Cancer Research, Garscube Estate, Glasgow G61 1BD, Scotland, and the || Laboratory of Biomedical Research, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113 0032, Japan

The human papillomavirus (HPV) transcription/replication factor E2 is essential for the life cycle of HPVs. E2 protein binds to DNA target sequences in the viral long control regions to regulate transcription of the viral genome. It also enhances viral DNA replication by interacting with the viral replication factor E1 and recruiting it to the origin of replication and may also play a more direct role in replication. The cellular proteins with which E2 interacts to carry out these functions are largely unknown. To identify these proteins a yeast two-hybrid screen was carried out with the transcription/replication domain of HPV16 E2. This screen identified several candidate interacting partners for E2 including TopBP1 (topoisomerase IIbeta -binding protein 1). TopBP1 has eight BRCA1 carboxyl-terminal domains that are found in proteins regulating the DNA damage response, transcription, and replication. Here we demonstrate that HPV16 E2 and TopBP1 interact in vitro and in vivo and that TopBP1 can enhance the ability of E2 to activate transcription and replication. This is the first time that TopBP1 has been shown to function as a transcriptional coactivator and that E2 interacts with TopBP1. Removal of the amino-terminal domain of TopBP1 abolishes coactivation of transcription and replication. This interaction may have functional consequences upon the viral life cycle.


* This work was supported in part by grants from the Association for International Cancer Research and the Scottish Hospital Endowment Research Trust.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a Biotechnology and Biological Sciences Research Council Industrial Cooperative Award in Science and Engineering studentship.

** Present address: Radiation Oncology, Case Western Reserve University, Cleveland, OH 44106.

Dagger Dagger To whom correspondence should be addressed. Tel.: 44-141-330-3155; Fax: 44-141-330-5602; E-mail: i.morgan@vet.gla.ac.uk.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


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