 Since XRCC4 is the key protein that enables interaction of LigIV to damaged DNA and therefore ligation of the ends, mutations in the XRCC4 gene were found to cause embryonic lethality in mice and developmental inhibition and immunodeficiency in humans.Furthermore, certain mutations in the XRCC4 gene are associated with an increased risk of cancer.DSBs are mainly caused by free radicals generated from ionizing radiation in the environment and from by-products released continually during cellular metabolism.