BRADFORD SCHOLARS

    • Sign in
    View Item 
    •   Bradford Scholars
    • Life Sciences
    • Life Sciences Publications
    • View Item
    •   Bradford Scholars
    • Life Sciences
    • Life Sciences Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Bradford ScholarsCommunitiesAuthorsTitlesSubjectsPublication DateThis CollectionAuthorsTitlesSubjectsPublication Date

    My Account

    Sign in

    HELP

    Bradford Scholars FAQsCopyright Fact SheetPolicies Fact SheetDeposit Terms and ConditionsDigital Preservation Policy

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    USP11 controls R-loops by regulating senataxin proteostasis

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    View/Open
    Published version (1.743Mb)
    Download
    Publication date
    2021
    Author
    Jurga, Mateusz
    Abugable, A.A.
    Goldman, Alastair S.H.
    El-Khamisy, Sherif F.
    Keyword
    R-loops
    SETX
    USP11
    KEAP1
    Genome instability
    Rights
    © 2021 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
    Peer-Reviewed
    Yes
    Open Access status
    Gold
    
    Metadata
    Show full item record
    Abstract
    R-loops are by-products of transcription that must be tightly regulated to maintain genomic stability and gene expression. Here, we describe a mechanism for the regulation of the Rloop- specific helicase, senataxin (SETX), and identify the ubiquitin specific peptidase 11 (USP11) as an R-loop regulator. USP11 de-ubiquitinates SETX and its depletion increases SETX K48-ubiquitination and protein turnover. Loss of USP11 decreases SETX steady-state levels and reduces R-loop dissolution. Ageing of USP11 knockout cells restores SETX levels via compensatory transcriptional downregulation of the E3 ubiquitin ligase, KEAP1. Loss of USP11 reduces SETX enrichment at KEAP1 promoter, leading to R-loop accumulation, enrichment of the endonuclease XPF and formation of double-strand breaks. Overexpression of KEAP1 increases SETX K48-ubiquitination, promotes its degradation and R-loop accumulation. These data define a ubiquitination-dependent mechanism for SETX regulation, which is controlled by the opposing activities of USP11 and KEAP1 with broad applications for cancer and neurological disease.
    URI
    http://hdl.handle.net/10454/18592
    Version
    Published version
    Citation
    Jurga M, Abugable AA, Goldman ASH et al (2021) USP11 controls R-loops by regulating senataxin proteostasis. Nature Communications. 12: 5156.
    Link to publisher’s version
    https://doi.org/10.1038/s41467-021-25459-w
    Type
    Article
    Collections
    Life Sciences Publications

    entitlement

     
    DSpace software (copyright © 2002 - 2022)  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.