Specific Roles of XRCC4 Paralogs PAXX and XLF during V(D)J Recombination.
Fiche publication
Date publication
septembre 2016
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr REINA-SAN-MARTIN Bernardo
Tous les auteurs :
Lescale C, Lenden Hasse H, Blackford AN, Balmus G, Bianchi JJ, Yu W, Bacoccina L, Jarade A, Clouin C, Sivapalan R, Reina-San-Martin B, Jackson SP, Deriano L
Lien Pubmed
Résumé
Paralog of XRCC4 and XLF (PAXX) is a member of the XRCC4 superfamily and plays a role in nonhomologous end-joining (NHEJ), a DNA repair pathway critical for lymphocyte antigen receptor gene assembly. Here, we find that the functions of PAXX and XLF in V(D)J recombination are masked by redundant joining activities. Thus, combined PAXX and XLF deficiency leads to an inability to join RAG-cleaved DNA ends. Additionally, we demonstrate that PAXX function in V(D)J recombination depends on its interaction with Ku. Importantly, we show that, unlike XLF, the role of PAXX during the repair of DNA breaks does not overlap with ATM and the RAG complex. Our findings illuminate the role of PAXX in V(D)J recombination and support a model in which PAXX and XLF function during NHEJ repair of DNA breaks, whereas XLF, the RAG complex, and the ATM-dependent DNA damage response promote end joining by stabilizing DNA ends.
Référence
Cell Rep. 2016 Sep;16(11):2967-79