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Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation-induced G1 arrest

Nature Genetics volume 19, pages 39–46 (1998)Cite this article

Abstract

Chromosome 3q alterations occur frequently in many types of tumours. In a genetic screen for loci present in rhabdomyosarcomas, we identified an isochromosome 3q [i(3q)], which inhibits muscle differentiation when transferred into myoblasts. The i(3q) inhibits MyoD function, resulting in a non-differentiating phenotype. Furthermore, the i(3q) induces a ‘cut’ phenotype, abnormal centrosome amplification, aneuploidy and loss of G1 arrest following γ-irradiation. Testing candidate genes within this region reveals that forced expression of ataxiatelangiectasia and rad3-related (ATR) results in a phenocopy of the i(3q). Thus, genetic alteration of ATR leads to loss of differentiation as well as cell-cycle abnormalities.

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Authors and Affiliations

  1. Vollum Institute, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon, 97201, USA

    Leslie Smith, Catherine Degnin & Mathew J. Thayer

  2. Department of Molecular and Medical Genetics, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon, 97201, USA

    Shu Jing Liu, Lisa Goodrich, David Jacobson & Mathew J. Thayer

  3. MRC Cell Mutation Unit, Sussex University, Palmer, BN1 9RR, UK

    Nicole Bentley & Antony Carr

  4. ICOS Corporation, 22021 20th Avenue SE, Bothell, Washington, 98021, USA

    Gail Flaggs, Kathleen Keegan & Merl Hoekstra

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  1. Leslie Smith
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Correspondence to Mathew J. Thayer.

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Smith, L., Liu, S., Goodrich, L. et al. Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation-induced G1 arrest. Nat Genet 19, 39–46 (1998). https://doi.org/10.1038/ng0598-39

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  • DOI: https://doi.org/10.1038/ng0598-39

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