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ATM stabilizes DNA double-strand-break complexes during V(D)J recombination.
- Source :
-
Nature [Nature] 2006 Jul 27; Vol. 442 (7101), pp. 466-70. Date of Electronic Publication: 2006 Jun 14. - Publication Year :
- 2006
-
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.
- Subjects :
- Animals
Ataxia Telangiectasia genetics
Ataxia Telangiectasia Mutated Proteins
B-Lymphocytes metabolism
Cell Cycle Proteins genetics
Cell Line
Chromosome Breakage genetics
DNA-Binding Proteins deficiency
DNA-Binding Proteins genetics
Mice
Protein Serine-Threonine Kinases deficiency
Protein Serine-Threonine Kinases genetics
Stem Cells metabolism
Tumor Suppressor Proteins deficiency
Tumor Suppressor Proteins genetics
Cell Cycle Proteins metabolism
DNA Damage
DNA Repair
DNA-Binding Proteins metabolism
Gene Rearrangement, B-Lymphocyte genetics
Protein Serine-Threonine Kinases metabolism
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 442
- Issue :
- 7101
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 16799570
- Full Text :
- https://doi.org/10.1038/nature04866