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

Cell Reports

Stéphane Audebert¹  Satish K. Tadi¹  Mauro Modesti¹  Sunetra Roy²  Katheryn Meek²  Carine Tellier-Lebègue³  Pascal Drevet³  Clément Nemoz³  Jean-Baptiste Charbonnier³ 

[1] Cancer Research Center of Marseille, CNRS UMR7258, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université UM105, 13273 Marseille, France;Department of Microbiology & Molecular Genetics, and Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA;Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, University Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette cedex, France;

关键词: DNA double-strand break repair;    NHEJ;    V(D)J recombination;    MMEJ;    PAXX;    XLF;    XRCC4;    Ku;    Ku70;    DNA ligase 4;   

DOI  :  10.1016/j.celrep.2016.09.026

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown