XRCC4/XLF Interaction Is Variably Required for DNA Repair and Is Not Required for Ligase IV Stimulation

• DOI: 10.1128/mcb.01503-14
• Publication Date: 2015-06-23T01:51:09Z
• Authors: Sunetra Roy; Abinadabe J. de Melo; Yao Xu; Satish K. Tadi; Aurélie Négrel; Eric Hendrickson; Mauro Modesti; Katheryn Meek
• Keywords: Non-homologous end joining

The classic nonhomologous end-joining (c-NHEJ) pathway is largely responsible for repairing double-strand breaks (DSBs) in mammalian cells. XLF stimulates the XRCC4/DNA ligase IV complex by an unknown mechanism. interacts with XRCC4 to form filaments of alternating and dimers that bridge DNA ends vitro, providing a mechanism which might stimulate ligation. Here, we characterize two mutants do not interact cannot or vitro. One mutant fully sufficient stimulating ligation XRCC4/Lig4 vitro; other not. This separation-of-function (which must function as homodimer) complements c-NHEJ deficits some XLF-deficient cell strains but others, suggesting variable requirement XRCC4/XLF interaction living To determine whether lack (and potential bridging) can be compensated factors, candidate repair factors were disrupted XLF- XRCC4-deficient loss either ATM newly described XRCC4/XLF-like factor, PAXX, accentuates XLF. However, case ATM/XLF (but PAXX/XLF loss), this reflects greater interaction.