IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms14959.html
   My bibliography  Save this article

A domain in human EXOG converts apoptotic endonuclease to DNA-repair exonuclease

Author

Listed:
  • Michal R. Szymanski

    (University of Texas Medical Branch
    Sealy Center for Structural Biology, University of Texas Medical Branch)

  • Wangsheng Yu

    (University of Texas Medical Branch
    Sealy Center for Structural Biology, University of Texas Medical Branch)

  • Aleksandra M. Gmyrek

    (University of Texas Medical Branch)

  • Mark A. White

    (Sealy Center for Structural Biology, University of Texas Medical Branch
    University of Texas Medical Branch)

  • Ian J. Molineux

    (University of Texas at Austin)

  • J. Ching Lee

    (Sealy Center for Structural Biology, University of Texas Medical Branch
    University of Texas Medical Branch)

  • Y. Whitney Yin

    (University of Texas Medical Branch
    Sealy Center for Structural Biology, University of Texas Medical Branch)

Abstract

Human EXOG (hEXOG) is a 5′-exonuclease that is crucial for mitochondrial DNA repair; the enzyme belongs to a nonspecific nuclease family that includes the apoptotic endonuclease EndoG. Here we report biochemical and structural studies of hEXOG, including structures in its apo form and in a complex with DNA at 1.81 and 1.85 Å resolution, respectively. A Wing domain, absent in other ββα-Me members, suppresses endonuclease activity, but confers on hEXOG a strong 5′-dsDNA exonuclease activity that precisely excises a dinucleotide using an intrinsic ‘tape-measure’. The symmetrical apo hEXOG homodimer becomes asymmetrical upon binding to DNA, providing a structural basis for how substrate DNA bound to one active site allosterically regulates the activity of the other. These properties of hEXOG suggest a pathway for mitochondrial BER that provides an optimal substrate for subsequent gap-filling synthesis by DNA polymerase γ.

Suggested Citation

  • Michal R. Szymanski & Wangsheng Yu & Aleksandra M. Gmyrek & Mark A. White & Ian J. Molineux & J. Ching Lee & Y. Whitney Yin, 2017. "A domain in human EXOG converts apoptotic endonuclease to DNA-repair exonuclease," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14959
    DOI: 10.1038/ncomms14959
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms14959
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms14959?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14959. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.