XLF (also called Cernunnos) interacts with the XRCC4-DNA ligase IV complex to promote DNA non-homologous end-joining. 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.