The DNA double strand breaks (DSBs) produced by free radicals generated during oxidative respiration, ionizing radiation, DNA replication, malfunction of recombination activating gene complex during V(D)J (variable region, diversity region-junction region) recombination in T and B lymphocytes are brought in closed proximity by Ku70-Ku80 heterodimer and kinase activity by DNA dependent protein kinase catalytic subunit (DNA-PKcs) of DNA-PK complex followed by its ligation by XRCC4-DNA ligase IV, SCID (Severe Combined Immunodeficiency) is associated with defective NHEJ repair system [15]. Here, LIG4 is linked to severe combined immunodeficiency.