InterPro domain: IPR038051

This N-terminal domain is structurally similar in XRCC4 and non-homologous end-joining factor 1, also known as XRCC4-like (XLF), consisting of seven-stranded antiparallel beta-sandwich with a helix-turn-helix motif inserted between beta-strands 4 and 5 [ 1 , 2 ].

XRCC4 is essential for non-homologous DNA end joining (NHDJ) in eukaryotes, which is required for double-strand break repair, and V(D)J recombination in immunoglobulin and T-cell receptor genes. XRCC4 forms a complex with DNA ligase IV, and acts as a regulatory element required for the stability and activity of the ligase. XRCC4 forms an elongated dumb-bell-like tetramer consisting of a C-terminal stalk that interacts with DNA ligase IV and an N-terminal globular head. The N-terminal head domain consists of a beta sandwich and a helix-turn-helix (HTH) motif, which may be involved in DNA binding [ 3 , 4 ].

1. Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ. EMBO J. 27, 290-300
2. XRCC4 protein interactions with XRCC4-like factor (XLF) create an extended grooved scaffold for DNA ligation and double strand break repair. J. Biol. Chem. 286, 32638-50
3. Crystal structure of the Xrcc4 DNA repair protein and implications for end joining. EMBO J. 19, 5962-70
4. Crystal structure of an Xrcc4-DNA ligase IV complex. Nat. Struct. Biol. 8, 1015-9