{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNHEJ1, also known as Cernunnos or XLF, is a core component of the nonhomologous end‐joining (NHEJ) pathway that repairs DNA double‐strand breaks. This factor directly interacts with the XRCC4–DNA ligase IV complex to stimulate the final ligation step and promote both the joining of noncohesive or mismatched DNA ends and the accurate completion of V(D)J recombination. Defects in NHEJ1 lead to marked radiosensitivity and immunodeficiency, as evidenced by clinical findings of microcephaly, growth retardation, and combined immunodeficiency in patients carrying loss‐of‐function mutations in its gene."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the mechanistic level, NHEJ1 functions by forming dynamic interactions with XRCC4 to assemble filamentous structures that bridge and align broken DNA ends. Structural and biophysical studies have revealed that its head‐to‐head interactions with XRCC4 are essential in creating a positively charged channel for DNA binding, thereby facilitating efficient gap filling and precise ligation without extensive nucleotide loss. These multimodal associations also contribute to allosteric regulation of the ligase complex and may help stabilize repair intermediates under different physiological conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its biochemical activity, NHEJ1 is critical for maintaining genomic stability during both replication and immune receptor diversification. Its role in facilitating gap filling during repair has broad implications—not only ensuring proper V(D)J recombination in developing lymphocytes but also protecting against chromosomal instability under conditions of replication stress. 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