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© Deriano Lab / Institut Pasteur
Chromosomes métaphasiques d’une cellule lymphoïde cancéreuse présentant une amplification des gènes Igh et c-myc
Publication : Molecular cell

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular cell - 10 Apr 2009

Deriano L, Stracker TH, Baker A, Petrini JH, Roth DB

Link to Pubmed [PMID] – 19362533

Mol. Cell 2009 Apr;34(1):13-25

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.

http://www.ncbi.nlm.nih.gov/pubmed/19362533