A multifaceted role for ATM in genome maintenance

Expert Rev Mol Med. 2003 Jun 20;5(16):1-21. doi: 10.1017/S1462399403006318.

Abstract

The pleiotropic nature of the clinical phenotypes of patients with ataxia-telangiectasia (A-T)--which encompass cerebellar degeneration (leading to ataxia), gonadal atrophy, and cancer predisposition--suggests multiple functions of the gene responsible for the disease. The ataxia-telangiectasia mutated gene product (ATM), whose loss of function is responsible for ataxia-telangiectasia, is a protein kinase that interacts with several substrates and is implicated in mitogenic signal transduction, chromosome condensation, meiotic recombination, cell-cycle control and telomere maintenance. This review focuses on the critical roles that ATM appears to play in cell-cycle checkpoints, DNA repair, telomere metabolism and oxidative stress, indicating how defects in these processes might lead to ataxia-telangiectasia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Ataxia Telangiectasia / etiology*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • DNA Repair
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Humans
  • Oxidative Stress
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology*
  • Telomere / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*

Substances

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