biostudies-literatureFattah FJNIA NIH HHSNational Cancer InstituteNCI NIH HHSNational Institutes of HealthNIGMS NIH HHS39-53https://www.ebi.ac.uk/biostudies/studies/S-EPMC3948327biostudies-literatureUnknown15Classic non-homologous end-joining (C-NHEJ) is required for the repair of radiation-induced DNA double-strand breaks (DSBs) in mammalian cells and plays a critical role in lymphoid V(D)J recombination. A core C-NHEJ component is the DNA ligase IV co-factor, Cernunnos/XLF (hereafter XLF). In patients, mutations in XLF cause predicted increases in radiosensitivity and deficits in immune function, but also cause other less well-understood pathologies including neural disorders. To characterize XLF function(s) in a defined genetic system, we used a recombinant adeno-associated virus-mediated gene targeting strategy to inactivate both copies of the XLF locus in the human HCT116 cell line. Analyses of XLF-null cells (which were viable) showed that they were highly sensitive to ionizing radiationDNA repairA role for XLF in DNA repair and recombination in human somatic cells.PMC3948327P30 CA77598R01 GM088351R01 CA154461P30 CA077598CA154461T32 AG029796GM088351Lichter NHendrickson EAKweon JFattah FJLee EHWang YWeisensel NKan YfalseA role for XLF in DNA repair and recombination in human somatic cells.Classic non-homologous end-joining (C-NHEJ) is required for the repair of radiation-induced DNA double-strand breaks (DSBs) in mammalian cells and plays a critical role in lymphoid V(D)J recombination. A core C-NHEJ component is the DNA ligase IV co-factor, Cernunnos/XLF (hereafter XLF). In patients, mutations in XLF cause predicted increases in radiosensitivity and deficits in immune function, but also cause other less well-understood pathologies including neural disorders. To characterize XLF function(s) in a defined genetic system, we used a recombinant adeno-associated virus-mediated gene targeting strategy to inactivate both copies of the XLF locus in the human HCT116 cell line. Analyses of XLF-null cells (which were viable) showed that they were highly sensitive to ionizing radiation2014-01-01T00:00:00Z2014 Mar2025-04-20T02:44:56.708Z2019-03-27T01:23:10ZS-EPMC39483272446173410.1016/j.dnarep.2013.12.006