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

First Author  Deriano L Year  2009
Journal  Mol Cell Volume  34
Issue  1 Pages  13-25
PubMed ID  19362533 Mgi Jnum  J:148280
Mgi Id  MGI:3844181 Doi  10.1016/j.molcel.2009.03.009
Citation  Deriano L, et al. (2009) Roles for NBS1 in alternative nonhomologous end-joining of V(D)J recombination intermediates. Mol Cell 34(1):13-25
abstractText  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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