This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wilkinson, D. E. Articles by Weller, S. K. Search for Related Content PubMed PubMed Citation Articles by Wilkinson, D. E. Articles by Weller, S. K.

 Previous Article  |  Next Article 

Journal of Virology, June 2005, p. 7162-7171, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7162-7171.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Inhibition of the Herpes Simplex Virus Type 1 DNA Polymerase Induces Hyperphosphorylation of Replication Protein A and Its Accumulation at S-Phase-Specific Sites of DNA Damage during Infection

Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, Connecticut 06030

Received 15 December 2004/ Accepted 1 February 2005

The treatment of mammalian cells with genotoxic substances can trigger DNA damage responses that include the hyperphosphorylation of replication protein A (RPA), a protein that plays key roles in the recognition, signaling, and repair of damaged DNA. We have previously reported that in the presence of a viral polymerase inhibitor, herpes simplex virus type 1 (HSV-1) infection induces the hyperphosphorylation of RPA (D. E. Wilkinson and S. K. Weller, J. Virol. 78:4783-4796, 2004). We initiated the present study to further characterize this genotoxic response to HSV-1 infection. Here we report that infection in the presence of polymerase inhibitors triggers an S-phase-specific response to DNA damage, as demonstrated by induction of the hyperphosphorylation of RPA and its accumulation within viral foci specific to the S phase of the cell cycle. This DNA damage response occurred in the presence of viral polymerase inhibitors and required the HSV-1 polymerase holoenzyme as well as the viral single-stranded-DNA binding protein. Treatment with an inhibitor of the viral helicase-primase did not induce the hyperphosphorylation of RPA or its accumulation in infected cells. Taken together, these results suggest that the S-phase-specific DNA damage response to infection is dependent on the specific inhibition of the polymerase. Finally, RPA hyperphosphorylation was not induced during productive infection, indicating that active viral replication does not trigger this potentially detrimental stress response.

This article has been cited by other articles:

• Conn, K. L., Hendzel, M. J., Schang, L. M. (2008). Linker Histones Are Mobilized during Infection with Herpes Simplex Virus Type 1. J. Virol. 82: 8629-8646 [Abstract] [Full Text]  
• Glauser, D. L., Strasser, R., Laimbacher, A. S., Saydam, O., Clement, N., Linden, R. M., Ackermann, M., Fraefel, C. (2007). Live Covisualization of Competing Adeno-Associated Virus and Herpes Simplex Virus Type 1 DNA Replication: Molecular Mechanisms of Interaction. J. Virol. 81: 4732-4743 [Abstract] [Full Text]  
• Wilkinson, D. E., Weller, S. K. (2006). Herpes simplex virus type I disrupts the ATR-dependent DNA-damage response during lytic infection. J. Cell Sci. 119: 2695-2703 [Abstract] [Full Text]