Nuclease involved in DNA non-homologous end joining (NHEJ); required for double-strand break repair and V(D)J recombination (   ). Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments ( ). V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs) ( ). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends ( ). These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively ( ). This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC ( , ). The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint . Also required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ ( , ).
Subcellular locations: Nucleus
Ubiquitously expressed, with highest levels in the kidney, lung, pancreas and placenta (at the mRNA level). Expression is not increased in thymus or bone marrow, sites of V(D)J recombination.