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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Walker, Laura M. Omi, Kazuo Q. Nussenzweig, Andre Mahowald, Grace K. Callen, Elsa Gapud, Eric J. Bredemeyer, Andrea Bednarski, Jeffrey J. Bassing, Craig H. Sleckman, Barry P. Dorsett, Yair Mckinnon, Peter J. Yin, Bu |
| Description | Author Affiliation: Gapud EJ ( Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.); |
| Abstract | Lymphocyte antigen receptor gene assembly occurs through the process of V(D)J recombination, which is initiated when the RAG endonuclease introduces DNA DSBs at two recombining gene segments to form broken DNA coding end pairs and signal end pairs. These paired DNA ends are joined by proteins of the nonhomologous end-joining (NHEJ) pathway of DSB repair to form a coding joint and signal joint, respectively. RAG DSBs are generated in G1-phase developing lymphocytes, where they activate the ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases to orchestrate diverse cellular DNA damage responses including DSB repair. Paradoxically, although Atm and DNA-PKcs both function during coding joint formation, Atm appears to be dispensible for signal joint formation; and although some studies have revealed an activity for DNA-PKcs during signal joint formation, others have not. Here we show that Atm and DNA-PKcs have overlapping catalytic activities that are required for chromosomal signal joint formation and for preventing the aberrant resolution of signal ends as potentially oncogenic chromosomal translocations. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 5 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Cycle Proteins Metabolism Chromosomes DNA-Activated Protein Kinase DNA-Binding Proteins Nuclear Proteins Protein-Serine-Threonine Kinases Tumor Suppressor Proteins Animals Ataxia Telangiectasia Mutated Proteins Mice Mice, SCID Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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