1. Academic Validation
  2. XRCC4's interaction with XLF is required for coding (but not signal) end joining

XRCC4's interaction with XLF is required for coding (but not signal) end joining

  • Nucleic Acids Res. 2012 Feb;40(4):1684-94. doi: 10.1093/nar/gkr1315.
Sunetra Roy 1 Sara N Andres Alexandra Vergnes Jessica A Neal Yao Xu Yaping Yu Susan P Lees-Miller Murray Junop Mauro Modesti Katheryn Meek
Affiliations

Affiliation

  • 1 College of Veterinary Medicine and Departments of Microbiology & Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, USA.
Abstract

XRCC4 and XLF are structurally related proteins important for DNA Ligase IV function. XRCC4 forms a tight complex with DNA Ligase IV while XLF interacts directly with XRCC4. Both XRCC4 and XLF form homodimers that can polymerize as heterotypic filaments independently of DNA Ligase IV. Emerging structural and in vitro biochemical data suggest that XRCC4 and XLF together generate a filamentous structure that promotes bridging between DNA molecules. Here, we show that ablating XRCC4's affinity for XLF results in DNA repair deficits including a surprising deficit in VDJ coding, but not signal end joining. These data are consistent with a model whereby XRCC4/XLF complexes hold DNA ends together--stringently required for coding end joining, but dispensable for signal end joining. Finally, DNA-PK phosphorylation of XRCC4/XLF complexes disrupt DNA bridging in vitro, suggesting a regulatory role for DNA-PK's phosphorylation of XRCC4/XLF complexes.

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