DNA repair protein XRCC4
Protein-coding gene in the species Homo sapiens / From Wikipedia, the free encyclopedia
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DNA repair protein XRCC4 (hXRCC4) also known as X-ray repair cross-complementing protein 4 is a protein that in humans is encoded by the XRCC4 gene. XRCC4 is also expressed in many other animals, fungi and plants.[5] hXRCC4 is one of several core proteins involved in the non-homologous end joining (NHEJ) pathway to repair DNA double strand breaks (DSBs).[6][7][8]
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 4 , by hXRCC4, with the aid of Cernunnos-XLF. DNA-PKcs and hXRCC4 are anchored to Ku70 / Ku80 heterodimer, which are bound to the DNA ends.[9]
Since hXRCC4 is the key protein that enables interaction of DNA ligase 4 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.[9] Furthermore, certain mutations in XRCC4 are associated with an increased risk of cancer.[10]