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Mol Cell. 2009 Apr 10;34(1):13-25. doi: 10.1016/j.molcel.2009.03.009.

Roles for NBS1 in alternative nonhomologous end-joining of V(D)J recombination intermediates.

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  • 1Department of Pathology, The Helen L and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine and , New York University School of Medicine, New York, NY 10016, USA.


Recent work has highlighted the importance of alternative, error-prone mechanisms for joining DNA double-strand breaks (DSBs) in mammalian cells. These noncanonical, nonhomologous end-joining (NHEJ) pathways threaten genomic stability but remain poorly characterized. The RAG postcleavage complex normally prevents V(D)J recombination-associated DSBs from accessing alternative NHEJ. Because the MRE11/RAD50/NBS1 complex localizes to RAG-mediated DSBs and possesses DNA end tethering, processing, and joining activities, we asked whether it plays a role in the mechanism of alternative NHEJ or participates in regulating access of DSBs to alternative repair pathways. We find that NBS1 is required for alternative NHEJ of hairpin coding ends, suppresses alternative NHEJ of signal ends, and promotes proper resolution of inversional recombination intermediates. These data demonstrate that the MRE11 complex functions at two distinct levels, regulating repair pathway choice (likely through enhancing the stability of DNA end complexes) and participating in alternative NHEJ of coding ends.

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