Breaking down cell cycle checkpoints and DNA repair during antigen receptor gene assembly.
Double-strand breaks (DSBs) are intermediates in several physiological processes including V(D)J and class switch recombination. They are also potent substrates for chromosomal translocations that arise as by-products of antigen receptor gene assembly in lymphocytes. ATM is one among several key proteins involved in the detection, signaling and repair of DNA breaks. Despite redundancies in DSB signaling pathways, it has recently been demonstrated that ATM deficient lymphocytes can survive and proliferate several generations in vitro and in vivo despite harboring terminally deleted chromosomes produced by V(D)J recombination. In this review, we discuss how two complementary genome maintenance functions mediated by ATM prevent lymphocytes from adapting to persistent DNA damage.
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360, USA. callene@mail.nih.gov
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D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011946:Receptors, Antigen / Q000235:genetics*; D011995:Recombination, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D045567:VDJ Recombinases
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011946:Receptors, Antigen; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D045567:VDJ Recombinases