ATM: genome stability, neuronal development, and cancer cross paths

Adv Cancer Res. 2001;83:209-54. doi: 10.1016/s0065-230x(01)83007-4.


One of the cornerstones of the web of signaling pathways governing cellular life and differentiation is the DNA damage response. It spans a complex network of pathways, ranging from DNA repair to modulation of numerous processes in the cell. DNA double-strand breaks (DSBs), which are formed as a result of genotoxic stress or normal recombinational processes, are extremely lethal lesions that rapidly mobilize this intricate defense system. The master controller that pilots cellular responses to DSBs is the ATM protein kinase, which turns on this network by phosphorylating key players in its various branches. ATM is the protein product of the gene mutated in the human genetic disorder ataxia-telangiectasia (A-T), which is characterized by neuronal degeneration, immunodeficiency, sterility, genomic instability, cancer predisposition, and radiation sensitivity. The clinical and cellular phenotype of A-T attests to the numerous roles of ATM, on the one hand, and to the link between the DNA damage response and developmental processes on the other hand. Recent studies of this protein and its effectors, combined with a thorough investigation of animal models of A-T, have led to new insights into the mode of action of this master controller of the DNA damage response. The evidence that ATM is involved in signaling pathways other than those related to damage response, particularly ones relating to cellular growth and differentiation, reinforces the multifaceted nature of this protein, in which genome stability, developmental processes, and cancer cross paths.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Cell Differentiation
  • DNA Damage
  • DNA-Binding Proteins
  • Genetic Predisposition to Disease
  • Models, Biological
  • Multigene Family
  • Mutation*
  • Neoplasms / genetics
  • Open Reading Frames
  • Oxidative Stress
  • Phenotype
  • Protein-Serine-Threonine Kinases / genetics*
  • Signal Transduction
  • Tumor Suppressor Proteins


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