DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair

Science. 2015 Jan 9;347(6218):185-188. doi: 10.1126/science.1261971.

Abstract

XRCC4 and XLF are two structurally related proteins that function in DNA double-strand break (DSB) repair. Here, we identify human PAXX (PAralog of XRCC4 and XLF, also called C9orf142) as a new XRCC4 superfamily member and show that its crystal structure resembles that of XRCC4. PAXX interacts directly with the DSB-repair protein Ku and is recruited to DNA-damage sites in cells. Using RNA interference and CRISPR-Cas9 to generate PAXX(-/-) cells, we demonstrate that PAXX functions with XRCC4 and XLF to mediate DSB repair and cell survival in response to DSB-inducing agents. Finally, we reveal that PAXX promotes Ku-dependent DNA ligation in vitro and assembly of core nonhomologous end-joining (NHEJ) factors on damaged chromatin in cells. These findings identify PAXX as a new component of the NHEJ machinery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Nuclear / metabolism*
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • DNA Breaks, Double-Stranded*
  • DNA End-Joining Repair*
  • DNA Repair Enzymes / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Ku Autoantigen
  • Protein Structure, Secondary
  • RNA Interference

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • NHEJ1 protein, human
  • PAXX protein, human
  • XRCC4 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen
  • DNA Repair Enzymes