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

Nat Genet. 1998 May;19(1):39-46. doi: 10.1038/ng0598-39.

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 gamma-irradiation. Testing candidate genes within this region reveals that forced expression of ataxia-telangiectasia 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aneuploidy*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics*
  • Cell Division
  • Chromosomes, Human, Pair 3
  • G1 Phase / radiation effects*
  • Humans
  • Isochromosomes
  • Multigene Family*
  • Muscles / cytology
  • MyoD Protein / antagonists & inhibitors*
  • MyoD Protein / physiology
  • Protein-Serine-Threonine Kinases*
  • Rhabdomyosarcoma / genetics
  • Rhabdomyosarcoma / pathology
  • Tumor Cells, Cultured

Substances

  • Cell Cycle Proteins
  • MyoD Protein
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases