The cellular protein MCM3AP is required for inhibition of cellular DNA synthesis by the IE86 protein of human cytomegalovirus.
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Publication Date
2012Journal Title
PLoS One
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Volume
7
Issue
10
Pages
e45686
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Poole, E., Bain, M., Teague, L., Takei, Y., Laskey, R., & Sinclair, J. (2012). The cellular protein MCM3AP is required for inhibition of cellular DNA synthesis by the IE86 protein of human cytomegalovirus.. PLoS One, 7 (10), e45686. https://doi.org/10.1371/journal.pone.0045686
Abstract
Like all DNA viruses, human cytomegalovirus (HCMV) infection is known to result in profound effects on host cell cycle. Infection of fibroblasts with HCMV is known to induce an advance in cell cycle through the G(0)-G(1) phase and then a subsequent arrest of cell cycle in early S-phase, presumably resulting in a cellular environment optimum for high levels of viral DNA replication whilst precluding replication of cellular DNA. Although the exact mechanisms used to arrest cell cycle by HCMV are unclear, they likely involve a number of viral gene products and evidence points to the ability of the virus to prevent licensing of cellular DNA synthesis. One viral protein known to profoundly alter cell cycle is the viral immediate early 86 (IE86) protein--an established function of which is to initially drive cells into early S phase but then inhibit cellular DNA synthesis. Here we show that, although IE86 interacts with the cellular licensing factor Cdt1, it does not inhibit licensing of cellular origins. Instead, IE86-mediated inhibition of cellular DNA synthesis requires mini-chromosome-maintenance 3 (MCM3) associated protein (MCM3AP), which can cause subsequent inhibition of initiation of cellular DNA synthesis in a licensing-independent manner.
Keywords
Cells, Cultured, Fibroblasts, Humans, Cytomegalovirus, Acetyltransferases, Intracellular Signaling Peptides and Proteins, Immediate-Early Proteins, Trans-Activators, RNA, Small Interfering, Transfection, Virus Replication, DNA Replication, Gene Expression, Plasmids, Host-Pathogen Interactions, HEK293 Cells, Cell Cycle Checkpoints
Sponsorship
Medical Research Council (G0701279)
Medical Research Council (G9202171)
Identifiers
External DOI: https://doi.org/10.1371/journal.pone.0045686
This record's URL: https://www.repository.cam.ac.uk/handle/1810/318141
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