DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes

Mol Cell. 1998 Oct;2(4):477-84. doi: 10.1016/s1097-2765(00)80147-1.


Nonhomologous DNA end joining (NHEJ) is the major pathway for repairing double-strand DNA breaks. V(D)J recombination is a double-strand DNA breakage and rejoining process that relies on NHEJ for the joining steps. Here we show that the targeted disruption of both DNA ligase IV alleles in a human pre-B cell line renders the cells sensitive to ionizing radiation and ablates V(D)J recombination. This phenotype can only be reversed by complementation with DNA ligase IV but not by expression of either of the remaining two ligases, DNA ligase I or III. Hence, DNA ligase IV is the activity responsible for the ligation step in NHEJ and in V(D)J recombination.

Publication types

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

MeSH terms

  • Alleles
  • B-Lymphocytes / cytology
  • B-Lymphocytes / enzymology*
  • B-Lymphocytes / radiation effects
  • Cells, Cultured
  • DNA Ligase ATP
  • DNA Ligases / genetics
  • DNA Ligases / metabolism*
  • DNA Nucleotidyltransferases / genetics
  • DNA Nucleotidyltransferases / metabolism*
  • DNA Repair / physiology*
  • DNA, Complementary
  • Genetic Complementation Test
  • Humans
  • Mutagenesis / physiology
  • Phenotype
  • VDJ Recombinases


  • DNA, Complementary
  • LIG1 protein, human
  • LIG4 protein, human
  • DNA Nucleotidyltransferases
  • VDJ Recombinases
  • DNA Ligases
  • DNA Ligase ATP