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The mechanism of inhibition of herpes simplex virus type 1 DNA replication by roscovitine Open Access


Other title
Herpes simplex virus
roscovitine OR Seliciclib OR cyc202
cyclin dependent kinase
Type of item
Degree grantor
University of Alberta
Author or creator
Newman, Emma
Supervisor and department
Schang, Luis (Biochemistry and Medical Microbiology and Immunology)
Examining committee member and department
Goping, Ing Swie (Biochemistry)
Schultz, Mike (Biochemistry)
Wang, Zhixiang (Cell Biology)
Department of Biochemistry

Date accepted
Graduation date
Master of Science
Degree level
Transcription and DNA replication of herpes simplex virus type 1 (HSV-1) occur in nuclear domains adjacent to structures named ND10. The HSV-1 single-stranded DNA binding protein ICP8 localizes to these nuclear domains to direct the assembly of the pre- and replication compartments. Inhibition of cyclin dependent kinases with roscovitine inhibits HSV-1 DNA replication, even in the presence of all required HSV-1 proteins, at an unidentified step. Here I show that roscovitine inhibits the localization of pre-expressed ICP8 to new replication sites. Therefore, the inhibition of HSV-1 DNA replication occurs at a step prior to initiation. I next evaluated the mechanisms of inhibition of proper ICP8 localization. ICP8 was extracted at lower salt concentrations from roscovitine-treated than untreated cells, but the affinity of ICP8 for ssDNA in vitro was not affected. I propose that roscovitine inhibits HSV-1 DNA replication by inhibiting DNA accessibility. I also discuss alternative mechanisms.
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