PAXX Is an Accessory c-NHEJ Factor that Associates with Ku70 and Has Overlapping Functions with XLF - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Cell Reports Année : 2016

PAXX Is an Accessory c-NHEJ Factor that Associates with Ku70 and Has Overlapping Functions with XLF

Résumé

In mammalian cells, classical non-homologous end joining (c-NHEJ) is critical for DNA double-strand break repair induced by ionizing radiation and during V(D)J recombination in developing B and T lymphocytes. Recently, PAXX was identified as a c-NHEJ core component. We report here that PAXX-deficient cells exhibit a cellular phenotype uncharacteristic of a deficiency in c-NHEJ core components. PAXX-deficient cells display normal sensitivity to radiomimetic drugs, are proficient in transient V(D)J recombination assays, and do not shift toward higher micro-homology usage in plasmid repair assays. Although PAXX-deficient cells lack c-NHEJ phenotypes, PAXX forms a stable ternary complex with Ku bound to DNA. Formation of this complex involves an interaction with Ku70 and requires a bare DNA extension for stability. Moreover, the relatively weak Ku-dependent stimulation of LIG4/XRCC4 activity by PAXX is unmasked by XLF ablation. Thus, PAXX plays an accessory role during c-NHEJ that is largely overlapped by XLF's function.
Fichier principal
Vignette du fichier
Tadi et al. Cell Reports 2016.pdf (2.26 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

inserm-01401845 , version 1 (23-11-2016)

Identifiants

Citer

Satish  K. Tadi, Carine Tellier-Lebègue, Clément Nemoz, Pascal Drevet, Stéphane Audebert, et al.. PAXX Is an Accessory c-NHEJ Factor that Associates with Ku70 and Has Overlapping Functions with XLF. Cell Reports, 2016, 17 (2), pp.541 - 555. ⟨10.1016/j.celrep.2016.09.026⟩. ⟨inserm-01401845⟩
146 Consultations
204 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More