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Originally published In Press as doi:10.1074/jbc.M005627200 on November 7, 2000

J. Biol. Chem., Vol. 276, Issue 4, 2905-2913, January 26, 2001
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Recombination during Early Herpes Simplex Virus Type 1 Infection Is Mediated by Cellular Proteins*

Xiao-Dan YaoDagger and Per Elias§

From the Dagger  Department of Molecular Biology and Genetics, College of Biological Science, University of Guelph, Guelph, Ontario N1G 2W1, Canada and the § Department of Medical Biochemistry, Göteborg University, Box 440, Göteborg SE 405 30, Sweden

Homologous recombination was examined in cells infected with herpes simplex virus type I. Circular and linear DNA with directly repeated sequences was introduced as recombination substrates into cells. Recombination was measured either by origin-dependent amplification of recombination products or by recombination-dependent expression of luciferase from a disrupted gene. Homologous recombination in baby hamster kidney cells converted linear DNA to circular templates for DNA replication and luciferase expression in the complete absence of virus. The products of homologous recombination were efficiently amplified by the viral replication apparatus. The efficiency of recombination was dependent on the structure of the substrate as well as the cell type. Linear DNA with the direct repeats at internal positions failed to recombine in Balb/c 3T3 cells and induced p53-dependent apoptosis. In contrast, linear DNA with directly repeated sequences precisely at the ends recombined and replicated in 3T3 cells. Homologous recombination in baby hamster kidney cells did not depend on the position of the repeated sequences. We conclude that homologous recombination is independent of viral gene functions and that it is likely to be carried out by cellular proteins. We suggest that homologous recombination between directly repeated sequences in the linear herpes simplex virus type 1 chromosome may help to avoid p53-dependent apoptosis and to promote viral DNA replication.


* This work was supported by Medical Research Council Grant K99-31X-12199-03C and Swedish Cancer Society Grant 2552-B97-11XAC.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.

To whom correspondence should be addressed. Tel.: 46-31-7733486; Fax: 46-31-416108; E-mail: per.elias@medkem.gu.se.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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