A noncatalytic function of the ligation complex during nonhomologous end joining

• DOI: 10.1083/jcb.201203128
• Publication Date: 2013-01-21T17:23:36Z
• Authors: Jessica Cottarel; Philippe Frit; Oriane Bombarde; Bernard Salles; Aurélie Négrel; Stéphanie Bernard; Penny A. Jeggo; Michael R. Lieber; Mauro Modesti; Patrick Calsou
• Keywords: Non-homologous end joining; Posttranslational modification

Nonhomologous end joining is the primary deoxyribonucleic acid (DNA) double-strand break repair pathway in multicellular eukaryotes. To initiate repair, Ku binds DNA ends and recruits DNA-dependent protein kinase (DNA-PK) catalytic subunit (DNA-PKcs) forming holoenzyme. Early synapsis associated with autophosphorylation. The XRCC4 (X4)–DNA Ligase IV (LIG4) complex (X4LIG4) executes final ligation promoted by Cernunnos (Cer)–X4-like factor (XLF). In this paper, using a cell-free system that recapitulates DNA-PKcs autophosphorylation, we found defect both activities human cell extracts lacking LIG4. LIG4 also stimulated autophosphorylation reconstitution assay purified components. We additionally uncovered LIG4-defective cells was corrected ectopic expression of catalytically dead Finally, our data support contribution Cer-XLF to unexpected early role joining. propose productive occurs formation supramolecular entity containing DNA-PK X4LIG4–Cer-XLF complexes on ends.