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The cellular protein MCM3AP is required for inhibition of cellular DNA synthesis by the IE86 protein of human cytomegalovirus.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Bain, Mark 
Teague, Linda 
Takei, Yoshinori 
Laskey, Ron 

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.

Description

Keywords

Acetyltransferases, Cell Cycle Checkpoints, Cells, Cultured, Cytomegalovirus, DNA Replication, Fibroblasts, Gene Expression, HEK293 Cells, Host-Pathogen Interactions, Humans, Immediate-Early Proteins, Intracellular Signaling Peptides and Proteins, Plasmids, RNA, Small Interfering, Trans-Activators, Transfection, Virus Replication

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

7

Publisher

Public Library of Science (PLoS)
Sponsorship
Medical Research Council (G0701279)
Medical Research Council (G9202171)