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Originally published In Press as doi:10.1074/jbc.M108316200 on November 15, 2001

J. Biol. Chem., Vol. 277, Issue 7, 5660-5666, February 15, 2002
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Activation of the Herpes Simplex Virus Type-1 Origin-binding Protein (UL9) by Heat Shock Proteins*

Nicolas Tanguy Le Gac and Paul E. BoehmerDagger

From the Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, Florida 33101-6129

Heat shock proteins participate in the initiation of DNA replication of different organisms by facilitating the assembly of initiation complexes. We have examined the effects of human heat shock proteins (Hsp40 and Hsp70) on the interaction of the herpes simplex virus type-1 initiator protein (UL9) with oriS, one of the viral origins of replication. Hsp40 and Hsp70 act substoichiometrically to increase the affinity of UL9 for oriS. The major contributor to this effect is Hsp40. Heat shock proteins also stimulate the ATPase activity of UL9 with oriS and increase opening of the origin. In contrast, heat shock proteins have no effect on the origin-independent activities of UL9 suggesting that their role is not merely in refolding denatured protein. These observations are consistent with a role for heat shock proteins in activating UL9 to efficiently initiate viral origin-dependent DNA replication. The action of heat shock proteins in this capacity is analogous to their role in activating the initiator proteins of other organisms.


* This work was supported by National Institutes of Health Grant GM62643 and American Heart Association Grant 0050973B.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.

Dagger To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, University of Miami School of Medicine, P.O. Box 016129, Miami, FL 33101-6129. Tel.: 305-243-2934; Fax: 305-243-3955; E-mail: pboehmer@molbio.med.miami.edu.


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