ATM stabilizes DNA double-strand-break complexes during V(D)J recombination

Academic Article

Abstract

  • The ATM (ataxia-telangiectasia mutated) protein kinase mediates early cellular responses to DNA double-strand breaks (DSBs) generated during metabolic processes or by DNA-damaging agents. ATM deficiency leads to ataxia-telangiectasia, a disease marked by lymphopenia, genomic instability and an increased predisposition to lymphoid malignancies with chromosomal translocations involving lymphocyte antigen receptor loci. ATM activates cell-cycle checkpoints and can induce apoptosis in response to DNA DSBs. However, defects in these pathways of the DNA damage response cannot fully account for the phenotypes of ATM deficiency. Here, we show that ATM also functions directly in the repair of chromosomal DNA DSBs by maintaining DNA ends in repair complexes generated during lymphocyte antigen receptor gene assembly. When coupled with the cell-cycle checkpoint and pro-apoptotic activities of ATM, these findings provide a molecular explanation for the increase in lymphoid tumours with translocations involving antigen receptor loci associated with ataxia-telangiectasia. © 2006 Nature Publishing Group.
  • Authors

    Published In

  • Nature  Journal
  • Digital Object Identifier (doi)

    Author List

  • Bredemeyer AL; Sharma GG; Huang CY; Helmink BA; Walker LM; Khor KC; Nuskey B; Sullivan KE; Pandita TK; Bassing CH
  • Start Page

  • 466
  • End Page

  • 470
  • Volume

  • 442
  • Issue

  • 7101