• Login
    View Item 
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Scholarly CommonsCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    About

    AboutCreative CommonsAugusta University LibrariesUSG Copyright Policy

    Statistics

    Display statistics

    Characterization of the dna ligase iv and xrcc4 complex in dna double-strand break repair

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Lee_Kyung-Jong_PhD_2002.pdf
    Size:
    7.416Mb
    Format:
    PDF
    Download
    Thumbnail
    Name:
    Lee_Kyung-Jong_PhD_2002.pdf
    Size:
    7.416Mb
    Format:
    PDF
    Download
    Authors
    Lee, Kyung-Jong
    Issue Date
    2002-11
    URI

    http://hdl.handle.net/10675.2/623217
    
    Metadata
    Show full item record
    Abstract
    DNA double-strand breaks (DSBs) are among the most lethal forms of DNA damage. The nonhomologous end-joining (NHEJ) pathway is the principal mechanism for repairing DSBs in mammalian cells. It is also required for V(D)J recombination. There are at least four essential proteins in this pathway. These include Ku protein, DNA-PKcs, and the DNA Ligase IV /XRCC4 (DNL IV /XRCC4) complex. This dissertation reports the determination of the quaternary structure of the DNL IV /XRCC4 complex, the mapping of a major human autoimmune epitope in XRCC4, the identification of DNAPKcs phosphorylation sites in XRCC4, and an investigation of the biochemical significance of XRCC4 phosph9rylation. Biochemical characterization shows that DNA Ligase IV and XRCC4 form a stable mixed heterotetramer. this is the·active fonn of the enzyme and is essential for in vitro DNA end joining in the presence of additional factors deriyed from cell extracts. Data shown here also demonstrate-that the DNL _IV /XRCC4 complex is a human autoantigen. The major autoimmune epitope maps to amino acids 251-266. This epitope coincid~~ with ~ever~i sites where'XRCC4_ is.ppteniially· modified in response to radiation or inflammation, _includi,ng a DNA~PKcs phosphorylation site at serine 260. Results raise the possibility that radiation-induced post-translational modifications contribute to development of an autoimmune response in susceptible individuals. Previous work has shown that DNA-PKcs kinase activity is required for NHEJ, but the critical physiological .target of this enzyme is not yet known. Current work shows that DNA-PKcs phosphorylates serine 318 ofXRCC4, in addition to the serine 260 site · described above. The p~esence of serine 260 increases phosphorylation at serine 31.8, suggesting that phosphorylation can occur sequentially. Mutation of serine 260 reduced DNA end-joining activity and sensitivity to the PI3 kinase inhibitor (L Y294002). These <lat~ provide preliminary evidence that phosphorylation ofXRCC4 by DNA-PKcs contributes to regulation of DNA repair.
    Affiliation
    School of Graduate Studies
    Collections
    Theses and Dissertations

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    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.