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Permanent link (DOI): https://doi.org/10.7939/R3ZX4C

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

Descriptions

Other title
Subject/Keyword
Herpes simplex virus
roscovitine OR Seliciclib OR cyc202
cyclin dependent kinase
Type of item
Thesis
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
Department of Biochemistry
Specialization

Date accepted
2011-03-04T21:01:16Z
Graduation date
2011-06
Degree
Master of Science
Degree level
Master's
Abstract
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.
Language
English
DOI
doi:10.7939/R3ZX4C
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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File title: Prefatory pages 2
File title: Prefatory pages
File author: Emma Newman
Page count: 199
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