This entry represents the DNA double-strand break repair and V(D)J recombination protein XRCC4, which is found in certain Metazoans, fungi and plants. XRCC4 binds to DNA, and to DNA ligase IV (LIG4) to form the LIG4-XRCC4 complex []. The LIG4-XRCC4 complex is responsible for the ligation step in the non-homologous end joining (NHEJ) pathway of DNA double-strand break repair. XRCC4 enhances the joining activity of LIG4. It is thought that XRCC4 and LIG4 are essential for alignment-based gap filling, as well as for final ligation of the breaks []. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.
This entry represents the DNA ligase IV (Lig4) sequences between the two BRCA1 C-terminal (BRCT) domains. Lig4 along with Xrcc4 functions in DNA non-homologous end joining. This process is required to mend double-strand breaks. Upon ligase binding to an Xrcc4 dimer, the helical tails unwind leading to a flat interaction surface [].
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 [, ].
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 [, ].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 β-sandwich with a helix-turn-helix motif inserted between β-strands 4 and 5 [, ].
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 C-terminal oligomerisation domain consists of oligomers of short identical helices that form parallel coiled-coils [, ].This superfamily also matches the C-terminal of the coiled-coil myosin heavy chain tail region. Muscle contraction is caused by sliding between the thick and thin filaments of the myofibril. Myosin is a major component of thick filaments and exists as a hexamer of 2 heavy chains [], 2 alkali light chains, and 2 regulatory light chains. The heavy chain can be subdivided into the N-terminal globular head and the C-terminal coiled-coil rod-like tail [].
The protein APLF (aprataxin and PNK-like factor or Xip1; ) is a nuclease involved in single-strand and double-strand DNA break repair []. It has endo- and exonuclease activities and contains a FHA (forkhead-associated) domain and zinc-finger-like CYR motifs []. APLF interacts with XRCC1 and XRCC4 via its FHA domain [, ].
XLF (also called Cernunnos) is involved in DNA nonhomologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. XLF and XRCC4 form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair []. It directly interacts with the XRCC4-Ligase IV complex and siRNA-mediated downregulation of XLF in human cell lines leads to radio-sensitivity and impaired DNA non-homologous end-joining []. XLF is homologous to the yeast non-homologous end-joining factor Nej1 [].
