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

Ulf Grawunder, David Zimmer, Sebastian Fugmann, Klaus Schwarz, Michael R. Lieber*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

292 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)477-484
Number of pages8
JournalMolecular Cell
Volume2
Issue number4
DOIs
StatePublished - 10 1998
Externally publishedYes

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