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 (Matt) Thayer

Research output: Contribution to journalArticle

70 Citations (Scopus)

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 - 1998

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Isochromosomes
Aneuploidy
Radiation
Phenotype
Centrosome
Genetic Loci
Rhabdomyosarcoma
Myoblasts
Cell Cycle
Chromosomes
Muscles
Genes
Neoplasms

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation-induced G1 arrest. / Smith, Leslie; Liu, Shu Jing; Goodrich, Lisa; Jacobson, David; Degnin, Catherine; Bentley, Nicole; Carr, Antony; Flaggs, Gail; Keegan, Kathleen; Hoekstra, Merl; Thayer, Mathew (Matt).

In: Nature Genetics, Vol. 19, No. 1, 1998, p. 39-46.

Research output: Contribution to journalArticle

Smith, L, Liu, SJ, Goodrich, L, Jacobson, D, Degnin, C, Bentley, N, Carr, A, Flaggs, G, Keegan, K, Hoekstra, M & Thayer, MM 1998, 'Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation-induced G1 arrest', Nature Genetics, vol. 19, no. 1, pp. 39-46. https://doi.org/10.1038/ng0598-39
Smith, Leslie ; Liu, Shu Jing ; Goodrich, Lisa ; Jacobson, David ; Degnin, Catherine ; Bentley, Nicole ; Carr, Antony ; Flaggs, Gail ; Keegan, Kathleen ; Hoekstra, Merl ; Thayer, Mathew (Matt). / Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation-induced G1 arrest. In: Nature Genetics. 1998 ; Vol. 19, No. 1. pp. 39-46.
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AU - Degnin, Catherine

AU - Bentley, Nicole

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AU - Hoekstra, Merl

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