Conversely, the hyper-radiosensitivity linked to the LIG4 syndrome is simply due to the loss of ligase IV function: while the RIANS appears to be normal in the LIG4-mutated cells, the ligase IV may not serve as substrate in cytoplasm, as the ligase IV protein remains in the nucleus even after the irradiation [12,22]. The gene discussed is LIG4; the disease is LIG4 syndrome.