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

@article{Bredemeyer2006ATMSD,
  title={ATM stabilizes DNA double-strand-break complexes during V(D)J recombination},
  author={Andrea L Bredemeyer and Girdhar G Sharma and Ching‐Yu Huang and Beth A Helmink and Laura M. Walker and Katrina C. Khor and Beth Nuskey and Kathleen E. Sullivan and Tej K. Pandita and Craig H. Bassing and Barry P. Sleckman},
  journal={Nature},
  year={2006},
  volume={442},
  pages={466-470}
}
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… Expand
ATM Prevents the Persistence and Propagation of Chromosome Breaks in Lymphocytes
TLDR
It is shown that a significant fraction of mature ATM-deficient lymphocytes contain telomere-deleted ends produced by failed end joining during V(D)J recombination that persist in peripheral lymphocytes for at least 2 weeks in vivo and are stable over several generations in vitro. Expand
Detecting ATM-dependent chromatin modification in DNA damage response.
TLDR
This review summarizes the multiple approaches used to discern the role of ATM and other associated proteins in chromatin modification in response to DNA damage and shows that ATM activation is tightly regulated by chromatin modifications. Expand
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TLDR
It is shown that during V(D)J recombination, MRN deficiency leads to the aberrant joining of Rag DSBs and to the accumulation of unrepaired coding ends, thus establishing a functional role for MRN in the repair of Rag-mediated DNA D SBs. Expand
Mediator of DNA Damage Checkpoint Protein 1 Facilitates V(D)J Recombination in Cells Lacking DNA Repair Factor XLF
TLDR
The findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular. Expand
ATM Damage Response and XLF Repair Factor are Functionally Redundant In Joining DNA Breaks
TLDR
It is shown that XLF, ATM and H2AX all have fundamental roles in processing and joining DNA ends during V(D)J recombination, but that these roles have been masked by unanticipated functional redundancies. Expand
Aberrant V(D)J Recombination: Misrepair of DNA Breaks and Implications For Lymphomagenesis.
Canonical non-homologous end joining (C-NHEJ), a major DNA double-strand break (DSB) repair pathway, is required for the repair of general DSBs as well as programmed breaks generated during antigenExpand
ATM deficiency impairs thymocyte maturation because of defective resolution of T cell receptor α locus coding end breaks
TLDR
A unified model for the two major clinical characteristics of ATM deficiency, defective T cell maturation and increased genomic instability, frequently affecting the TCRα locus is proposed. Expand
Concurrent V(D)J recombination and DNA end instability increase interchromosomal trans-rearrangements in ATM-deficient thymocytes
TLDR
TCR trans-rearrangements are not the result of trans-synaptic complex formation, but they are instead because of unstable cis synaptic complexes that form simultaneously at distinct TCR loci, indicating that ATM function extends beyond timely resolution of DNA breaks. Expand
The Role for the DSB Response Pathway in Regulating Chromosome Translocations.
In response to DNA double strand breaks (DSB), mammalian cells activate the DNA Damage Response (DDR), a network of factors that coordinate their detection, signaling and repair. Central to thisExpand
Breaking down cell cycle checkpoints and DNA repair during antigen receptor gene assembly
TLDR
This review discusses how two complementary genome maintenance functions mediated by ATM prevent lymphocytes from adapting to persistent DNA damage. Expand
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Routine surveillance of intermediates in V(D)J recombination by ATM helps suppress potentially oncogenic translocations when repair fails, and it is suggested that ATM phosphorylates target proteins in situ. Expand
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TLDR
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