Non-homologous end joining (NHEJ)

Non-homologous end joining (NHEJ) is a multi-protein biochemical pathway, not a discrete molecular target, that repairs DNA double-strand breaks by directly ligating broken DNA ends without the requirement for a homologous template[1][3][4]. Central to NHEJ are protein complexes including the Ku70/80 heterodimer, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4, DNA ligase IV, XLF/Cernunnos, Artemis, and others[2][3][7]. NHEJ is the principal pathway for double-strand break repair in mammalian cells and functions throughout the cell cycle, particularly when homologous recombination is unavailable[1][4][7]. It is essential for maintaining genomic stability, generating immune diversity through V(D)J recombination, and enabling class switch recombination in immunoglobulin and T cell receptor genes[2][7]. NHEJ’s flexibility allows it to repair a wide variety of DNA end configurations but can be error-prone, leading to small insertions or deletions and sometimes chromosomal translocations that are hallmarks of cancer cells[1][7]. Defective NHEJ leads to radiosensitivity, immunodeficiency, and increased cancer susceptibility[3][7]. Because NHEJ is a pathway, not a single molecular species (receptor, enzyme, etc.), it is not a direct drug target in the traditional sense. However, individual components of NHEJ (e.g. DNA-PKcs, Ligase IV, Ku70/80) are considered therapeutic targets in oncology and immunology research. Note: This entry ("Non-homologous end joining") refers to a cellular pathway/process, not a protein, gene, or druggable molecular target. For drug discovery or molecular targeting, information should be requested for specific NHEJ protein components such as "DNA-dependent protein kinase catalytic subunit (DNA-PKcs)," "XRCC4," or "DNA ligase IV"[2][3][7].

Other names

NHEJnonhomologous DNA end joiningnonhomologous end-joining pathway