DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination (      ). Acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks (DSBs) ( , ). Associates with NHEJ1/XLF to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (  , ). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other . The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors . Plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed (  , ). XRCC4 stabilizes LIG4, regulates its subcellular localization and enhances LIG4's joining activity (   ). Binding of the LIG4-XRCC4 subcomplex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (, ). Promotes displacement of PNKP from processed strand break termini (, ).
Acts as an activator of the phospholipid scramblase activity of XKR4 . This form, which is generated upon caspase-3 (CASP3) cleavage, translocates into the cytoplasm and interacts with XKR4, thereby promoting phosphatidylserine scramblase activity of XKR4 and leading to phosphatidylserine exposure on apoptotic cell surface .
Subcellular locations: Nucleus, Chromosome
Localizes to site of double-strand breaks.
Subcellular locations: Cytoplasm
Translocates from the nucleus to the cytoplasm following cleavage by caspase-3 (CASP3).
Widely expressed.