Nonhomologous End Joining Factor 1 (NHEJ1)

Double-strand breaks (DSBs) result from genotoxic stresses and are among the most toxic DNA lesions. NHEJ1 is a DNA repair factor essential for the nonhomologous end-joining (NHEJ) pathway, which preferentially mediates repair of DSBs. Failure to repair DSBs results in genetic instability, developmental delay, and immunodeficiency.The predicted 299-amino acid Cernunnos protein shares 74% identity with its mouse homolog. RT-PCR analysis detected ubiquitous expression. Immunofluorescence microscopy showed a predominantly nuclear localization in transfected fibroblasts.Downregulation of either XRCC4 or XLF resulted in defective DNA DSB repair, and downregulation of XLF led to prolonged phosphorylation of H2AX (H2AFX) following irradiation.