IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms10399.html
   My bibliography  Save this article

Defective DNA single-strand break repair is responsible for senescence and neoplastic escape of epithelial cells

Author

Listed:
  • Joe Nassour

    (Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies
    Present address: The Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 Noth Torrey Pines Road, La Jolla, California 92037, USA)

  • Sébastien Martien

    (Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies)

  • Nathalie Martin

    (Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies)

  • Emeric Deruy

    (Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies)

  • Elisa Tomellini

    (Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies
    Present address: Molecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer, University of Montreal, Pavillon Marcel-Coutu 2950, chemin de Polytechnique, Montréal, Quebec H3T1J4, Canada)

  • Nicolas Malaquin

    (Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies
    Present address: Centre de Recherche du CHUM, Institut du Cancer de Montréal, 900 rue Saint Denis, Montréal, Quebec H2X09A, Canada)

  • Fatima Bouali

    (Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies)

  • Laure Sabatier

    (Commissariat à l'Energie Atomique (CEA), Laboratoire de Radiobiologie et Oncologie (LRO), 18 route du Panorama - BP6)

  • Nicolas Wernert

    (Institute of Pathology, University of Bonn)

  • Sébastien Pinte

    (Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies
    Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia Antipolis, CNRS, UMR7284, INSERM U108, Faculty of Medecine of Nice; CHU of Nice
    CHU of Nice)

  • Eric Gilson

    (Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia Antipolis, CNRS, UMR7284, INSERM U108, Faculty of Medecine of Nice; CHU of Nice
    CHU of Nice)

  • Albin Pourtier

    (Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies)

  • Olivier Pluquet

    (Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies)

  • Corinne Abbadie

    (Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Targeted Therapies)

Abstract

The main characteristic of senescence is its stability which relies on the persistence of DNA damage. We show that unlike fibroblasts, senescent epithelial cells do not activate an ATM-or ATR-dependent DNA damage response (DDR), but accumulate oxidative-stress-induced DNA single-strand breaks (SSBs). These breaks remain unrepaired because of a decrease in PARP1 expression and activity. This leads to the formation of abnormally large and persistent XRCC1 foci that engage a signalling cascade involving the p38MAPK and leading to p16 upregulation and cell cycle arrest. Importantly, the default in SSB repair also leads to the emergence of post-senescent transformed and mutated precancerous cells. In human-aged skin, XRCC1 foci accumulate in the epidermal cells in correlation with a decline of PARP1, whereas DDR foci accumulate mainly in dermal fibroblasts. These findings point SSBs as a DNA damage encountered by epithelial cells with aging which could fuel the very first steps of carcinogenesis.

Suggested Citation

  • Joe Nassour & Sébastien Martien & Nathalie Martin & Emeric Deruy & Elisa Tomellini & Nicolas Malaquin & Fatima Bouali & Laure Sabatier & Nicolas Wernert & Sébastien Pinte & Eric Gilson & Albin Pourtie, 2016. "Defective DNA single-strand break repair is responsible for senescence and neoplastic escape of epithelial cells," Nature Communications, Nature, vol. 7(1), pages 1-16, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10399
    DOI: 10.1038/ncomms10399
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10399
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms10399?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Haichao Zhao & Jia Li & Zhongsheng You & Howard D. Lindsay & Shan Yan, 2024. "Distinct regulation of ATM signaling by DNA single-strand breaks and APE1," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    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:7:y:2016:i:1:d:10.1038_ncomms10399. 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.