Competition between PARP-1 and Ku70 control the decision between high-fidelity and mutagenic DNA repair

DNA Repair (Amst). 2011 Mar 7;10(3):338-43. doi: 10.1016/j.dnarep.2010.12.005. Epub 2011 Jan 20.


Affinity maturation of antibodies requires a unique process of targeted mutation that allows changes to accumulate in the antibody genes while the rest of the genome is protected from off-target mutations that can be oncogenic. This targeting requires that the same deamination event be repaired either by a mutagenic or a high-fidelity pathway depending on the genomic location. We have previously shown that the BRCT domain of the DNA-damage sensor PARP-1 is required for mutagenic repair occurring in the context of IgH and IgL diversification in the chicken B cell line DT40. Here we show that immunoprecipitation of the BRCT domain of PARP-1 pulls down Ku70 and the DNA-PK complex although the BRCT domain of PARP-1 does not bind DNA, suggesting that this interaction is not DNA dependent. Through sequencing the IgL variable region in PARP-1(-/-) cells that also lack Ku70 or Lig4, we show that Ku70 or Lig4 deficiency restores GCV to PARP-1(-/-) cells and conclude that the mechanism by which PARP-1 is promoting mutagenic repair is by inhibiting high-fidelity repair which would otherwise be mediated by Ku70 and Lig4.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Nuclear / metabolism*
  • Biocatalysis
  • Cell Line
  • DNA Damage
  • DNA Ligase ATP
  • DNA Ligases / metabolism
  • DNA Repair / genetics*
  • DNA-Activated Protein Kinase / metabolism
  • DNA-Binding Proteins / metabolism*
  • Gene Conversion
  • Humans
  • Ku Autoantigen
  • Mutagenesis / genetics*
  • Nuclear Proteins / metabolism
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / chemistry
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Structure, Tertiary


  • Antigens, Nuclear
  • DNA-Binding Proteins
  • LIG4 protein, human
  • Nuclear Proteins
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen
  • DNA Ligases
  • DNA Ligase ATP