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Updated: Sep 20, 2026

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
Distinct pathways of nonhomologous end joining that are differentially regulated by DNA-dependent protein
Durga Udayakumar1, Catherine L Bladen, Farlyn Z Hudson
1Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Abstract:
Nonhomologous end joining is the most common mechanism of DNA double-strand break repair in human cells. Here we show that nonhomologous end joining can occur by two biochemically distinct pathways. One requires a fraction containing the Mre11-Rad50-NBS1 complex. The other requires a fraction containing a novel, approximately 200-kDa factor that does not correspond to any of the previously described double-strand break repair proteins. The two pathways converge, sharing a common requirement for the DNA ligase IV-XRCC4 complex to catalyze the final step of phosphodiester bond formation. Whereas the Mre11-Rad50-NBS1-dependent pathway does not require, and may be inhibited by, DNA-dependent protein kinase-mediated phosphorylation, the new pathway depends on this phosphorylation for release from a DNA-dependent protein kinase-mediated reaction checkpoint. The existence of two distinct pathways, which are differentially regulated by the DNA-dependent protein kinase, provides a possible explanation for the selective repair defects seen in DNA-dependent protein kinase-deficient mutants.
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