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

Leslie Smith, Shu Jing Liu, Lisa Goodrich, David Jacobson, Catherine Degnin, Nicole Bentley, Antony Carr, Gail Flaggs, Kathleen Keegan, Merl Hoekstra, Mathew J. Thayer

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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.

Original languageEnglish (US)
Pages (from-to)39-46
Number of pages8
JournalNature genetics
Volume19
Issue number1
DOIs
StatePublished - Jun 8 1998

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ASJC Scopus subject areas

  • Genetics

Cite this

Smith, L., Liu, S. J., Goodrich, L., Jacobson, D., Degnin, C., Bentley, N., Carr, A., Flaggs, G., Keegan, K., Hoekstra, M., & Thayer, M. J. (1998). Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation-induced G1 arrest. Nature genetics, 19(1), 39-46. https://doi.org/10.1038/ng0598-39