Essential and perilous: V(D)J recombination and DNA damage checkpoints in lymphocyte precursors

Semin Immunol. 1997 Jun;9(3):199-206. doi: 10.1006/smim.1997.0072.

Abstract

V(D)J recombination generates a diverse array of antigen-binding specificities, but breakage and re-joining of DNA segments have grave implications for the maintenance of genomic stability and oncogenic risk. Exposure of eukaryotic cells to genotoxic agents activates a DNA damage checkpoint that induces cell-cycle arrest and DNA repair, or apoptosis. We discuss several lines of evidence implicating DNA-dependent protein kinase (DNA-PK), and the gene mutated in ataxia telangiectasia (ATM), two mammalian homologues of yeast DNA damage-checkpoint genes, in regulating the response to intrinsic DNA damage that occurs during V(D)J recombination.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Nuclear*
  • Ataxia Telangiectasia / genetics
  • Cell Cycle
  • DNA Damage*
  • DNA Helicases*
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins / genetics
  • Hematopoietic Stem Cells / immunology
  • Humans
  • Ku Autoantigen
  • Lymphocytes / immunology*
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics
  • Receptors, Antigen / genetics*
  • Recombination, Genetic*
  • Saccharomyces cerevisiae Proteins*
  • Severe Combined Immunodeficiency / genetics

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Receptors, Antigen
  • Saccharomyces cerevisiae Proteins
  • high affinity DNA-binding factor, S cerevisiae
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • Protein Serine-Threonine Kinases
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen