Nonhomologous end joining and V(D)J recombination require an additional factor
| Autor: | Kostas G. Manolis, T. O. Harville, Penny A. Jeggo, Yan Dai, L. A. Hanakahi, Boris Kysela, Markus Stumm, Stephen C. West, Enriqueta Riballo, Marjorie A. Oettinger |
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| Rok vydání: | 2003 |
| Předmět: |
DNA
Complementary Time Factors Ku80 DNA Ligases DNA Repair DNA repair Immunoblotting Biology DNA Ligase ATP Catalytic Domain Tumor Cells Cultured Animals Humans VDJ Recombinases Cells Cultured chemistry.chemical_classification Ku70 DNA ligase Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction fungi V(D)J recombination Immunologic Deficiency Syndromes Dose-Response Relationship Radiation Fibroblasts Biological Sciences DNA repair protein XRCC4 Molecular biology Protein Structure Tertiary DNA-Binding Proteins Non-homologous end joining enzymes and coenzymes (carbohydrates) chemistry Rad50 embryonic structures DNA Nucleotidyltransferases Peptides DNA Damage Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences. 100:2462-2467 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | DNA nonhomologous end-joining (NHEJ) is the major pathway for repairing DNA double-strand breaks in mammalian cells. It also functions to carry out rearrangements at the specialized breaks introduced during V(D)J recombination. Here, we describe a patient with T−B−severe combined immunodeficiency, whose cells have defects closely resembling those of NHEJ-defective rodent cells. Cells derived from this patient show dramatic radiosensitivity, decreased double-strand break rejoining, and reduced fidelity in signal and coding joint formation during V(D)J recombination. Detailed examination indicates that the patient is defective neither in the known factors involved in NHEJ in mammals (Ku70, Ku80, DNA-dependent protein kinase catalytic subunit, Xrcc4, DNA ligase IV, or Artemis) nor in the Mre11/Rad50/Nbs1 complex, whose homologue inSaccharomyces cerevisiaefunctions in NHEJ. These results provide strong evidence that additional activities are crucial for NHEJ and V(D)J recombination in mammals. |
| Databáze: | OpenAIRE |
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