IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v421y2003i6922d10.1038_nature01368.html
   My bibliography  Save this article

DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation

Author

Listed:
  • Christopher J. Bakkenist

    (St Jude Children's Research Hospital)

  • Michael B. Kastan

    (St Jude Children's Research Hospital)

Abstract

The ATM protein kinase, mutations of which are associated with the human disease ataxia–telangiectasia, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer or higher-order multimer, with the kinase domain bound to a region surrounding serine 1981 that is contained within the previously described ‘FAT’ domain. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. Most ATM molecules in the cell are rapidly phosphorylated on this site after doses of radiation as low as 0.5 Gy, and binding of a phosphospecific antibody is detectable after the introduction of only a few DNA double-strand breaks in the cell. Activation of the ATM kinase seems to be an initiating event in cellular responses to irradiation, and our data indicate that ATM activation is not dependent on direct binding to DNA strand breaks, but may result from changes in the structure of chromatin.

Suggested Citation

  • Christopher J. Bakkenist & Michael B. Kastan, 2003. "DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation," Nature, Nature, vol. 421(6922), pages 499-506, January.
    • Handle: RePEc:nat:nature:v:421:y:2003:i:6922:d:10.1038_nature01368
    DOI: 10.1038/nature01368
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature01368
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature01368?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Huimin Zhang & Yun Xiong & Dan Su & Chao Wang & Mrinal Srivastava & Mengfan Tang & Xu Feng & Min Huang & Zhen Chen & Junjie Chen, 2022. "TDP1-independent pathways in the process and repair of TOP1-induced DNA damage," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. 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.
    3. Rut Molinuevo & Julien Menendez & Kora Cadle & Nabeela Ariqat & Marie Klaire Choy & Cayla Lagousis & Gwen Thomas & Catherine Strietzel & J. W. Bubolz & Lindsay Hinck, 2024. "Physiological DNA damage promotes functional endoreplication of mammary gland alveolar cells during lactation," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Zhang, L.W. & Cheng, Y.M. & Liew, K.M., 2014. "Mathematical modeling of p53 pulses in G2 phase with DNA damage," Applied Mathematics and Computation, Elsevier, vol. 232(C), pages 1000-1010.
    5. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    6. Sylvain V Costes & Artem Ponomarev & James L Chen & David Nguyen & Francis A Cucinotta & Mary Helen Barcellos-Hoff, 2007. "Image-Based Modeling Reveals Dynamic Redistribution of DNA Damage into Nuclear Sub-Domains," PLOS Computational Biology, Public Library of Science, vol. 3(8), pages 1-12, August.
    7. Salvatore Terrazzino & Sarah Cargnin & Letizia Deantonio & Carla Pisani & Laura Masini & Pier Luigi Canonico & Armando A Genazzani & Marco Krengli, 2019. "Impact of ATM rs1801516 on late skin reactions of radiotherapy for breast cancer: Evidences from a cohort study and a trial sequential meta-analysis," PLOS ONE, Public Library of Science, vol. 14(11), pages 1-21, November.

    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:nature:v:421:y:2003:i:6922:d:10.1038_nature01368. 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.