• Login
    View Item 
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of eScholarship@UMassChanCommunitiesPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywordsThis CollectionPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywords

    My Account

    LoginRegister

    Help

    AboutSubmission GuidelinesData Deposit PolicySearchingAccessibilityTerms of UseWebsite Migration FAQ

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    An E2F1-mediated DNA damage response contributes to the replication of human cytomegalovirus

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    journal.ppat.1001342.pdf
    Size:
    948.1Kb
    Format:
    PDF
    Download
    Authors
    E., Xiaofei
    Pickering, Mary Theresa
    Debatis, Michelle E.
    Castillo, Jonathan Patrick
    Lagadinos, Alexander
    Wang, Shixia
    Lu, Shan
    Kowalik, Timothy F.
    UMass Chan Affiliations
    Program in Immunology and Virology
    Department of Microbiology and Physiological Systems
    Department of Medicine, Department of Infectious Diseases and Immunology
    Document Type
    Journal Article
    Publication Date
    2011-05-12
    Keywords
    DNA Damage
    E2F1 Transcription Factor
    Cytomegalovirus
    Genetics and Genomics
    Immunology and Infectious Disease
    Life Sciences
    Medicine and Health Sciences
    
    Metadata
    Show full item record
    Abstract
    DNA damage resulting from intrinsic or extrinsic sources activates DNA damage responses (DDRs) centered on protein kinase signaling cascades. The usual consequences of inducing DDRs include the activation of cell cycle checkpoints together with repair of the damaged DNA or induction of apoptosis. Many DNA viruses elicit host DDRs during infection and some viruses require the DDR for efficient replication. However, the mechanism by which DDRs are activated by viral infection is poorly understood. Human cytomegalovirus (HCMV) infection induces a DDR centered on the activation of ataxia telangiectasia mutated (ATM) protein kinase. Here we show that HCMV replication is compromised in cells with inactivated or depleted ATM and that ATM is essential for the host DDR early during infection. Likewise, a downstream target of ATM phosphorylation, H2AX, also contributes to viral replication. The ATM-dependent DDR is detected as discrete, nuclear gammaH2AX foci early in infection and can be activated by IE proteins. By 24 hpi, gammaH2AX is observed primarily in HCMV DNA replication compartments. We identified a role for the E2F1 transcription factor in mediating this DDR and viral replication. E2F1, but not E2F2 or E2F3, promotes the accumulation of gammaH2AX during HCMV infection or IE protein expression. Moreover, E2F1 expression, but not the expression of E2F2 or E2F3, is required for efficient HCMV replication. These results reveal a novel role for E2F1 in mediating an ATM-dependent DDR that contributes to viral replication. Given that E2F activity is often deregulated by infection with DNA viruses, these observations raise the possibility that an E2F1-mediated mechanism of DDR activation may be conserved among DNA viruses.
    Source
    E X, Pickering MT, Debatis M, Castillo J, Lagadinos A, et al. (2011) An E2F1-Mediated DNA Damage Response Contributes to the Replication of Human Cytomegalovirus. PLoS Pathog 7(5): e1001342. doi:10.1371/journal.ppat.1001342. Link to article on publisher's site
    DOI
    10.1371/journal.ppat.1001342
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/39551
    PubMed ID
    21589897
    Notes

    Co-author Alexander Lagadinos is a student in the Immunology and Virology Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

    Related Resources
    Link to Article in PubMed
    Rights
    Copyright: © 2011 E et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.ppat.1001342
    Scopus Count
    Collections
    UMass Chan Faculty and Researcher Publications

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Lamar Soutter Library, UMass Chan Medical School | 55 Lake Avenue North | Worcester, MA 01655 USA
    Quick Guide | escholarship@umassmed.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.