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Science 8 December 2000:
Vol. 290. no. 5498, pp. 1962 - 1964
DOI: 10.1126/science.290.5498.1962
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Reports

Response to RAG-Mediated V(D)J Cleavage by NBS1 and gamma -H2AX

Hua Tang Chen,1* Avinash Bhandoola,1* Michael J. Difilippantonio,2* Jie Zhu,1 Martin J. Brown,1 Xuguang Tai,1 Emmy P. Rogakou,3 Tilmann M. Brotz,1 William M. Bonner,3 Thomas Ried,2 André Nussenzweig1dagger

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 gamma -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 gamma -H2AX form nuclear foci that colocalize with the T cell receptor alpha  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 gamma -H2AX may be important for preventing oncogenic translocations.

1 Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
2 Genetics Department, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
3 Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: andre_nussenzweig{at}nih.gov

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Science. ISSN 0036-8075 (print), 1095-9203 (online)