IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms14015.html
   My bibliography  Save this article

Telomeres in ICF syndrome cells are vulnerable to DNA damage due to elevated DNA:RNA hybrids

Author

Listed:
  • Shira Sagie

    (Molecular Medicine Laboratory, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion)

  • Shir Toubiana

    (Molecular Medicine Laboratory, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion)

  • Stella R. Hartono

    (University of California)

  • Hagar Katzir

    (Molecular Medicine Laboratory, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion)

  • Aya Tzur-Gilat

    (Molecular Medicine Laboratory, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion)

  • Shany Havazelet

    (Molecular Medicine Laboratory, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion)

  • Claire Francastel

    (Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate, CNRS UMR7216)

  • Guillaume Velasco

    (Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate, CNRS UMR7216)

  • Frédéric Chédin

    (University of California)

  • Sara Selig

    (Molecular Medicine Laboratory, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion)

Abstract

DNA:RNA hybrids, nucleic acid structures with diverse physiological functions, can disrupt genome integrity when dysregulated. Human telomeres were shown to form hybrids with the lncRNA TERRA, yet the formation and distribution of these hybrids among telomeres, their regulation and their cellular effects remain elusive. Here we predict and confirm in several human cell types that DNA:RNA hybrids form at many subtelomeric and telomeric regions. We demonstrate that ICF syndrome cells, which exhibit short telomeres and elevated TERRA levels, are enriched for hybrids at telomeric regions throughout the cell cycle. Telomeric hybrids are associated with high levels of DNA damage at chromosome ends in ICF cells, which are significantly reduced with overexpression of RNase H1. Our findings suggest that abnormally high TERRA levels in ICF syndrome lead to accumulation of telomeric hybrids that, in turn, can result in telomeric dysfunction.

Suggested Citation

  • Shira Sagie & Shir Toubiana & Stella R. Hartono & Hagar Katzir & Aya Tzur-Gilat & Shany Havazelet & Claire Francastel & Guillaume Velasco & Frédéric Chédin & Sara Selig, 2017. "Telomeres in ICF syndrome cells are vulnerable to DNA damage due to elevated DNA:RNA hybrids," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14015
    DOI: 10.1038/ncomms14015
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms14015
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms14015?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_ncomms14015. 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.