Response to RAG-Mediated V(D)J Cleavage by NBS1 and γ-H2AX
- 8 December 2000
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 290 (5498) , 1962-1964
- https://doi.org/10.1126/science.290.5498.1962
Abstract
Genetic disorders affecting cellular responses to DNA damage are characterized by high rates of translocations involving antigen receptor loci and increased susceptibility to lymphoid malignancies. We report that the Nijmegen breakage syndrome protein (NBS1) and histone γ-H2AX, which associate with irradiation-induced DNA double-strand breaks (DSBs), are also found at sites of V(D)J (variable, diversity, joining) recombination–induced DSBs. In developing thymocytes, NBS1 and γ-H2AX form nuclear foci that colocalize with the T cell receptor α locus in response to recombination activating gene (RAG) protein–mediated V(D)J cleavage. Our results suggest that surveillance of T cell receptor recombination intermediates by NBS1 and γ-H2AX may be important for preventing oncogenic translocations.Keywords
This publication has 27 references indexed in Scilit:
- Essential and perilous: V(D)J recombination and DNA damage checkpoints in lymphocyte precursorsSeminars in Immunology, 1997
- Identification of V(D)J recombination coding end intermediates in normal thymocytesJournal of Molecular Biology, 1997
- Characterization of coding ends in thymocytes of scid mice: Implications for the mechanism of V(D)J recombinationImmunity, 1995
- Impairment of V(D)J Recombination in Double-Strand Break Repair MutantsScience, 1993
- Exclusion and inclusion of α and β T cell receptor allelesCell, 1992
- Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumoursNature, 1992
- RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangementCell, 1992
- Thymocyte Expression of RAG-1 and RAG-2: Termination by T Cell Receptor Cross-LinkingScience, 1991
- Inhibition of T Cell Receptor Expression and Function in Immature CD4 + cD8 + Cells by CD4Science, 1990
- Normal Development of Mice Deficient in β 2 M, MCClass I Proteins, and CD8 + T CellsScience, 1990