Linking double-stranded DNA breaks to the recombination activating gene complex directs repair to the nonhomologous end-joining pathway

Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17046-51. doi: 10.1073/pnas.0610928104. Epub 2007 Oct 15.

Abstract

Two major DNA repair pathways, nonhomologous end-joining (NHEJ) and homologous recombination (HR), repair double-stranded DNA breaks (DSBs) in all eukaryotes. Additionally, several alternative end-joining pathways (or subpathways) have been reported that characteristically use short-sequence homologies at the DNA ends to facilitate joining. How a cell chooses which DNA repair pathway to use (at any particular DSB) is a central and largely unanswered question. For one type of DSB, there is apparently no choice. DSBs mediated by the lymphocyte-specific recombination activating gene (RAG) endonuclease are repaired virtually exclusively by NHEJ. Here we demonstrate that non-RAG-mediated DSBs can be similarly forced into the NHEJ pathway by physical association with the RAG endonuclease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Nuclear
  • Cell Survival
  • DNA Breaks, Double-Stranded*
  • DNA Repair*
  • DNA-Activated Protein Kinase / deficiency
  • DNA-Binding Proteins / deficiency
  • Homeodomain Proteins / metabolism*
  • Ku Autoantigen
  • Multiprotein Complexes / metabolism
  • Plasmids / metabolism
  • Protein Binding
  • Recombination, Genetic

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Multiprotein Complexes
  • RAG-1 protein
  • DNA-Activated Protein Kinase
  • Ku Autoantigen