• Login
    View Item 
    •   Home
    • Office of Sponsored Research (OSR)
    • KAUST Funded Research
    • Publications Acknowledging KAUST Support
    • View Item
    •   Home
    • Office of Sponsored Research (OSR)
    • KAUST Funded Research
    • Publications Acknowledging KAUST Support
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of KAUSTCommunitiesIssue DateSubmit DateThis CollectionIssue DateSubmit Date

    My Account

    Login

    Quick Links

    Open Access PolicyORCID LibguidePlumX LibguideSubmit an Item

    Statistics

    Display statistics

    Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Type
    Article
    Authors
    Reymer, A.
    Frykholm, K.
    Morimatsu, K.
    Takahashi, M.
    Norden, B.
    KAUST Grant Number
    KUK-11-008-23
    Date
    2009-07-08
    Online Publication Date
    2009-07-08
    Print Publication Date
    2009-08-11
    Permanent link to this record
    http://hdl.handle.net/10754/599767
    
    Metadata
    Show full item record
    Abstract
    To get mechanistic insight into the DNA strand-exchange reaction of homologous recombination, we solved a filament structure of a human Rad51 protein, combining molecular modeling with experimental data. We build our structure on reported structures for central and N-terminal parts of pure (uncomplexed) Rad51 protein by aid of linear dichroism spectroscopy, providing angular orientations of substituted tyrosine residues of Rad51-dsDNA filaments in solution. The structure, validated by comparison with an electron microscopy density map and results from mutation analysis, is proposed to represent an active solution structure of the nucleo-protein complex. An inhomogeneously stretched double-stranded DNA fitted into the filament emphasizes the strategic positioning of 2 putative DNA-binding loops in a way that allows us speculate about their possibly distinct roles in nucleo-protein filament assembly and DNA strand-exchange reaction. The model suggests that the extension of a single-stranded DNA molecule upon binding of Rad51 is ensured by intercalation of Tyr-232 of the L1 loop, which might act as a docking tool, aligning protein monomers along the DNA strand upon filament assembly. Arg-235, also sitting on L1, is in the right position to make electrostatic contact with the phosphate backbone of the other DNA strand. The L2 loop position and its more ordered compact conformation makes us propose that this loop has another role, as a binding site for an incoming double-stranded DNA. Our filament structure and spectroscopic approach open the possibility of analyzing details along the multistep path of the strand-exchange reaction.
    Citation
    Reymer A, Frykholm K, Morimatsu K, Takahashi M, Norden B (2009) Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy. Proceedings of the National Academy of Sciences 106: 13248–13253. Available: http://dx.doi.org/10.1073/pnas.0902723106.
    Sponsors
    We thank Professor Edward H. Egelman (University of Virginia, Charlottesville, VA) for kindly providing us with the surface map of a 3D reconstruction of a HsRad51 filament electron micrograph and Dr. Axelle Renodon-Cornière for performing the recombinase activity measurements. This work was supported by King Abdullah University of Science and Technology Grant KUK-11-008-23 and the Association pour la Recherche sur le Cancer (M.T.).
    Publisher
    Proceedings of the National Academy of Sciences
    Journal
    Proceedings of the National Academy of Sciences
    DOI
    10.1073/pnas.0902723106
    PubMed ID
    19587234
    PubMed Central ID
    PMC2726390
    ae974a485f413a2113503eed53cd6c53
    10.1073/pnas.0902723106
    Scopus Count
    Collections
    Publications Acknowledging KAUST Support

    entitlement

    Related articles

    • Ca2+ improves organization of single-stranded DNA bases in human Rad51 filament, explaining stimulatory effect on gene recombination.
    • Authors: Fornander LH, Frykholm K, Reymer A, Renodon-Cornière A, Takahashi M, Nordén B
    • Issue date: 2012 Jun
    • Visualizing the assembly of human Rad51 filaments on double-stranded DNA.
    • Authors: Prasad TK, Yeykal CC, Greene EC
    • Issue date: 2006 Oct 27
    • Structural analysis of the human Rad51 protein-DNA complex filament by tryptophan fluorescence scanning analysis: transmission of allosteric effects between ATP binding and DNA binding.
    • Authors: Renodon-Cornière A, Takizawa Y, Conilleau S, Tran V, Iwai S, Kurumizaka H, Takahashi M
    • Issue date: 2008 Nov 14
    • Roles of the human Rad51 L1 and L2 loops in DNA binding.
    • Authors: Matsuo Y, Sakane I, Takizawa Y, Takahashi M, Kurumizaka H
    • Issue date: 2006 Jul
    • Real-time assembly and disassembly of human RAD51 filaments on individual DNA molecules.
    • Authors: van der Heijden T, Seidel R, Modesti M, Kanaar R, Wyman C, Dekker C
    • Issue date: 2007
    DSpace software copyright © 2002-2021  DuraSpace
    Quick Guide | Contact Us | KAUST University Library
    Open Repository is a service hosted 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. For anonymous users the allowed maximum amount is 50 search results.

    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.