XRCC4

DNA repair protein XRCC4 also known as X-ray repair cross-complementing protein 4 or XRCC4 is a protein that in humans is encoded by the XRCC4 gene. In addition to humans, the XRCC4 protein is also expressed in many other metazoans, fungi and in plants. The X-ray repair cross-complementing protein 4 is one of several core proteins involved in the non-homologous end joining (NHEJ) pathway to repair DNA double strand breaks (DSBs). NHEJ requires two main components to achieve successful completion. The first component is the cooperative binding and phosphorylation of artemis by the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs). Artemis cleaves the ends of damaged DNA to prepare it for ligation. The second component involves the bridging of DNA to DNA Ligase IV (LigIV), by XRCC4, with the aid of Cernunos-XLF. DNA-PKcs and XRCC4 are anchored to Ku70 / Ku80 heterodimer, which are bound to the DNA ends. 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.