Splitting the ATM: distinct repair and checkpoint defects in ataxia-telangiectasia

Trends Genet. 1998 Aug;14(8):312-6. doi: 10.1016/s0168-9525(98)01511-x.

Abstract

Ataxia-telangiectasia (A-T) is an autosomal recessive human disorder that, because of its multisystem nature, is of interest to scientists and clinicians from many disciplines. A-T patients have defects in the neurological and immune systems, telangiectasia in the eyes and face, and are, in addition, cancer-prone and radiation-sensitive. A-T cell lines have a range of diverse phenotypes including sensitivity to ionizing radiation and defects in cell-cycle checkpoint control. The ATM protein is a member of the PI 3-kinase-like superfamily, and it has been widely accepted that A-T cells represent mammalian cell-cycle checkpoint mutants and that the radiation sensitivity is a consequence of this defect. However, several lines of evidence suggest that A-T cells have distinct repair and checkpoint defects. A-T cells therefore appear to harbour dual checkpoint/repair defects. Here, we review the evidence supporting this contention and consider its implications for an analysis of the A-T phenotype.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Animals
  • Ataxia Telangiectasia / complications
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia / metabolism
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • DNA Repair / genetics
  • DNA-Binding Proteins
  • Humans
  • Mice
  • Mice, Knockout
  • Mice, SCID
  • Mutation
  • Neoplasms / etiology
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Phenotype
  • Protein Serine-Threonine Kinases*
  • Proteins / genetics*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Atm protein, mouse
  • Protein Serine-Threonine Kinases