ATM-dependent DNA damage surveillance in T-cell development and leukemogenesis: the DSB connection

Immunol Rev. 2006 Feb;209:142-58. doi: 10.1111/j.0105-2896.2006.00361.x.


The immune system is capable of recognizing and eliminating an enormous array of pathogens due to the extremely diverse antigen receptor repertoire of T and B lymphocytes. However, the development of lymphocytes bearing receptors with unique specificities requires the generation of programmed double strand breaks (DSBs) coupled with bursts of proliferation, rendering lymphocytes susceptible to mutations contributing to oncogenic transformation. Consequently, mechanisms responsible for monitoring global genomic integrity must be activated during lymphocyte development to limit the oncogenic potential of antigen receptor locus recombination. Mutations in ATM (ataxia-telangiectasia mutated), a kinase that coordinates DSB monitoring and the response to DNA damage, result in impaired T-cell development and predispose to T-cell leukemia. Here, we review recent evidence providing insight into the mechanisms by which ATM promotes normal lymphocyte development and protects from neoplastic transformation.

Publication types

  • Review

MeSH terms

  • Animals
  • Ataxia Telangiectasia / enzymology
  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia / immunology
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • DNA / genetics
  • DNA Damage*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Rearrangement, T-Lymphocyte
  • Genomic Instability
  • Humans
  • Immune System Diseases / genetics
  • Immune System Diseases / immunology
  • Leukemia, T-Cell / enzymology
  • Lymphoma, T-Cell / enzymology
  • Lymphopoiesis / physiology*
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / pathology
  • Tumor Suppressor Proteins / deficiency
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*
  • VDJ Recombinases


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