title: 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.
authors.affiliation: Cancer Research Center of Marseille, CNRS UMR7258, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université UM105, 13273 Marseille, France.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Tadi
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, University Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette cedex, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Tellier-Lebègue
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, University Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette cedex, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Nemoz
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, University Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Drevet
authors.affiliation: Cancer Research Center of Marseille, CNRS UMR7258, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université UM105, 13273 Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Audebert
authors.affiliation: Department of Microbiology & Molecular Genetics, and Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Sunetra
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Microbiology & Molecular Genetics, and Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Katheryn
authors.initials: K
authors.lastname: Meek
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, University Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette cedex, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Charbonnier
authors.affiliation: 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.
authors.forename: Mauro
authors.initials: M
authors.lastname: Modesti
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D000072200:Ku Autoantigen / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D060152:V(D)J Recombination / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C508551:NHEJ1 protein, human; C000595075:PAXX protein, human; D000072200:Ku Autoantigen; D045643:DNA Repair Enzymes
keywords: DNA double-strand break repair; DNA ligase 4; Ku; Ku70; MMEJ; NHEJ; PAXX; V(D)J recombination; XLF; XRCC4