Similar to human DNA damage repair deficiency syndromes, such as AT and Seckel syndromes, Xrcc5−/− mice have neurodevelopmental defects, associated with unrepaired DNA breaks and extensive neuronal apoptosis during cortical development, as well as severe combined immunodeficiency due to the failure to repair RAG1/2-induced DNA breaks and rearrangements in developing lymphocytes (35). Here, RAG1 is linked to immunodeficiency disease.