PARP-3 and APLF function together to accelerate nonhomologous end-joining

Mol Cell. 2011 Jan 7;41(1):33-45. doi: 10.1016/j.molcel.2010.12.006.


PARP-3 is a member of the ADP-ribosyl transferase superfamily of unknown function. We show that PARP-3 is stimulated by DNA double-strand breaks (DSBs) in vitro and functions in the same pathway as the poly (ADP-ribose)-binding protein APLF to accelerate chromosomal DNA DSB repair. We implicate PARP-3 in the accumulation of APLF at DSBs and demonstrate that APLF promotes the retention of XRCC4/DNA ligase IV complex in chromatin, suggesting that PARP-3 and APLF accelerate DNA ligation during nonhomologous end-joining (NHEJ). Consistent with this, we show that class switch recombination in Aplf(-/-) B cells is biased toward microhomology-mediated end-joining, a pathway that operates in the absence of XRCC4/DNA ligase IV, and that the requirement for PARP-3 and APLF for NHEJ is circumvented by overexpression of XRCC4/DNA ligase IV. These data identify molecular roles for PARP-3 and APLF in chromosomal DNA double-strand break repair reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Cell Line
  • DNA Breaks, Double-Stranded
  • DNA Repair / physiology
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Gene Deletion
  • Humans
  • Mice
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphoproteins / physiology*
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Poly(ADP-ribose) Polymerases / physiology*
  • Poly-ADP-Ribose Binding Proteins
  • Recombinant Fusion Proteins / physiology


  • Carrier Proteins
  • Cell Cycle Proteins
  • Phosphoproteins
  • Poly-ADP-Ribose Binding Proteins
  • Recombinant Fusion Proteins
  • PARP3 protein, human
  • Poly(ADP-ribose) Polymerases
  • Parp2 protein, mouse
  • APLF protein, human
  • APLF protein, mouse
  • DNA-(Apurinic or Apyrimidinic Site) Lyase