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Cell Rep. 2016 Oct 4;17(2):541-555. doi: 10.1016/j.celrep.2016.09.026.

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

Author information

1
Cancer Research Center of Marseille, CNRS UMR7258, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université UM105, 13273 Marseille, France.
2
Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, University Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette cedex, France.
3
Department of Microbiology & Molecular Genetics, and Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
4
Cancer Research Center of Marseille, CNRS UMR7258, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université UM105, 13273 Marseille, France. Electronic address: mauro.modesti@inserm.fr.

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.

KEYWORDS:

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

PMID:
27705800
DOI:
10.1016/j.celrep.2016.09.026
[Indexed for MEDLINE]
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