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

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


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.

MeSH terms

  • B-Lymphocytes / metabolism
  • DNA Breaks, Double-Stranded
  • DNA End-Joining Repair / genetics*
  • DNA Repair / genetics
  • DNA Repair Enzymes / genetics*
  • DNA Repair Enzymes / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • HCT116 Cells
  • Humans
  • Ku Autoantigen / chemistry
  • Ku Autoantigen / genetics*
  • Ku Autoantigen / metabolism
  • T-Lymphocytes / metabolism
  • V(D)J Recombination / genetics


  • DNA-Binding Proteins
  • NHEJ1 protein, human
  • PAXX protein, human
  • Ku Autoantigen
  • DNA Repair Enzymes