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

Abstract : 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.
Type de document :
Article dans une revue
Cell Reports , Elsevier Inc, 2016, 17 (2), pp.541 - 555. 〈10.1016/j.celrep.2016.09.026〉
Liste complète des métadonnées

Littérature citée [49 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01401845
Contributeur : Mauro Modesti <>
Soumis le : mercredi 23 novembre 2016 - 19:05:06
Dernière modification le : mercredi 20 juin 2018 - 11:54:02

Fichier

Tadi et al. Cell Reports 2016....
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Citation

Satish  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 , Elsevier Inc, 2016, 17 (2), pp.541 - 555. 〈10.1016/j.celrep.2016.09.026〉. 〈inserm-01401845〉

Partager

Métriques

Consultations de la notice

86

Téléchargements de fichiers

108