Depletion of cellular pre-replication complex factors results in increased human cytomegalovirus DNA replication.
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Publication Date
2012Journal Title
PLoS One
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Volume
7
Issue
5
Pages
e36057
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Braun, T. E., Poole, E., & Sinclair, J. (2012). Depletion of cellular pre-replication complex factors results in increased human cytomegalovirus DNA replication.. PLoS One, 7 (5), e36057. https://doi.org/10.1371/journal.pone.0036057
Abstract
Although HCMV encodes many genes required for the replication of its DNA genome, no HCMV-encoded orthologue of the origin binding protein, which has been identified in other herpesviruses, has been identified. This has led to speculation that HCMV may use other viral proteins or possibly cellular factors for the initiation of DNA synthesis. It is also unclear whether cellular replication factors are required for efficient replication of viral DNA during or after viral replication origin recognition. Consequently, we have asked whether cellular pre-replication (pre-RC) factors that are either initially associated with cellular origin of replication (e.g. ORC2), those which recruit other replication factors (e.g. Cdt1 or Cdc6) or those which are subsequently recruited (e.g. MCMs) play any role in the HCMV DNA replication. We show that whilst RNAi-mediated knock-down of these factors in the cell affects cellular DNA replication, as predicted, it results in concomitant increases in viral DNA replication. These data show that cellular factors which initiate cellular DNA synthesis are not required for the initiation of replication of viral DNA and suggest that inhibition of cellular DNA synthesis, in itself, fosters conditions which are conducive to viral DNA replication.
Keywords
Fibroblasts, Humans, Cytomegalovirus, DNA-Binding Proteins, Viral Proteins, RNA, Small Interfering, DNA, Viral, DNA Replication, Replication Origin, Origin Recognition Complex, Gene Knockdown Techniques
Sponsorship
Medical Research Council (G0701279)
Medical Research Council (G9202171)
Identifiers
External DOI: https://doi.org/10.1371/journal.pone.0036057
This record's URL: https://www.repository.cam.ac.uk/handle/1810/318137
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