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  • The EMBO Journal (2000) 19, 463 - 471
  • doi:10.1093/emboj/19.3.463



There is a Corrigendum (February 2000) associated with this Article.

The controlling role of ATM in homologous recombinational repair of DNA damage

Ciaran Morrison1,2, Eiichiro Sonoda3,4, Noriaki Takao5, Akira Shinohara6, Ken-ichi Yamamoto5 and Shunichi Takeda1,3,4

  1. Bayer Chair Department of Molecular Immunology and Allergology, Faculty of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
  2. Present address: Institute of Cell and Molecular Biology, King's Buildings, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, UK
  3. CREST, Japan Science and Technology, Faculty of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku Kyoto 606-8501, Japan
  4. Department of Radiation Genetics, Faculty of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
  5. Department of Molecular Pathology, Cancer Research Institute, Kanazawa University, Ishikawa 920-0934, Japan
  6. Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA

Correspondence to:

Shunichi Takeda, E-mail: stakeda@rg1.rg.med.kyoto-u.ac.jp

Received 20 July 1999; Accepted 25 November 1999; Revised 23 November 1999

The human genetic disorder ataxia telangiectasia (A-T), caused by mutation in the ATM gene, is characterized by chromosomal instability, radiosensitivity and defective cell cycle checkpoint activation. DNA double-strand breaks (dsbs) persist in A-T cells after irradiation, but the underlying defect is unclear. To investigate ATM's interactions with dsb repair pathways, we disrupted ATM along with other genes involved in the principal, complementary dsb repair pathways of homologous recombination (HR) or non-homologous end-joining (NHEJ) in chicken DT40 cells. ATM-/- cells show altered kinetics of radiation-induced Rad51 and Rad54 focus formation. Ku70-deficient (NHEJ-) ATM-/- chicken DT40 cells show radiosensitivity and high radiation-induced chromosomal aberration frequencies, while Rad54-defective (HR-) ATM-/- cells show only slightly elevated aberration levels after irradiation, placing ATM and HR on the same pathway. These results reveal that ATM defects impair HR-mediated dsb repair and may link cell cycle checkpoints to HR activation.

  • Keywords:

    • ataxia telangiectasia,
    • double strand breaks,
    • non-homologous end-joining,
    • nuclear foci,
    • recombination