Response to RAG-mediated V (D) J cleavage by NBS1 and γ-H2AX

HT Chen, A Bhandoola, MJ Difilippantonio, J Zhu… - Science, 2000 - science.org
HT Chen, A Bhandoola, MJ Difilippantonio, J Zhu, MJ Brown, X Tai, EP Rogakou, TM Brotz
Science, 2000science.org
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 …
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.
AAAS