title: Splitting the ATM: distinct repair and checkpoint defects in ataxia-telangiectasia.
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.
authors.affiliation: MRC Cell Mutation Unit, University of Sussex, Brighton, UK. p.a.jeggo@sussex.ac.uk
authors.forename: P A
authors.initials: PA
authors.lastname: Jeggo
authors.forename: A M
authors.initials: AM
authors.lastname: Carr
authors.forename: A R
authors.initials: AR
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009154:Mutation; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases