Nonhomologous DNA end-joining for repair of DNA double-strand breaks

J Biol Chem. 2018 Jul 6;293(27):10512-10523. doi: 10.1074/jbc.TM117.000374. Epub 2017 Dec 14.


Nonhomologous DNA end-joining (NHEJ) is the predominant double-strand break (DSB) repair pathway throughout the cell cycle and accounts for nearly all DSB repair outside of the S and G2 phases. NHEJ relies on Ku to thread onto DNA termini and thereby improve the affinity of the NHEJ enzymatic components consisting of polymerases (Pol μ and Pol λ), a nuclease (the Artemis·DNA-PKcs complex), and a ligase (XLF·XRCC4·Lig4 complex). Each of the enzymatic components is distinctive for its versatility in acting on diverse incompatible DNA end configurations coupled with a flexibility in loading order, resulting in many possible junctional outcomes from one DSB. DNA ends can either be directly ligated or, if the ends are incompatible, processed until a ligatable configuration is achieved that is often stabilized by up to 4 bp of terminal microhomology. Processing of DNA ends results in nucleotide loss or addition, explaining why DSBs repaired by NHEJ are rarely restored to their original DNA sequence. Thus, NHEJ is a single pathway with multiple enzymes at its disposal to repair DSBs, resulting in a diversity of repair outcomes.

Keywords: DNA endonuclease; DNA repair; DNA-dependent serine/threonine protein kinase (DNA-PK); NHEJ; double-stranded DNA breaks; nucleic acid enzymology; protein structure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA Breaks, Double-Stranded*
  • DNA End-Joining Repair*
  • Humans
  • Ku Autoantigen / metabolism*


  • Ku Autoantigen

Associated data

  • PDB/1JEQ
  • PDB/1JEY
  • PDB/5LUQ
  • PDB/5Y3R
  • PDB/3W1B
  • PDB/3II6
  • PDB/3RWR
  • PDB/3WTF