DNA Ligase IV (D5N5N) Rabbit Monoclonal Antibody#14649,Cell Signaling Technology (CST),14649

DNA double-strand breaks (DSBs) are potentially hazardous lesions that can be induced by ionizing radiation (IR), radiomimetic chemicals, or DNA replication inhibitors. Cells detect and repair DSBs through two distinct but partly overlapping signaling pathways, nonhomologous end joining (NHEJ) and homologous recombination (HR). DNA repair through the HR pathway is restricted to S and G2 phases of the cell cycle, while NHEJ can occur during any cell cycle phase. Defects in both pathways have been associated with human disease, including cancer (1).DNA repair through the NHEJ pathway involves a core group of proteins that includes the Ku heterodimer, DNA-PKcs, DNA ligase IV, XRCC4, and XLF. XLF interacts with XRCC4 and promotes the ligation of DNA strands by DNA ligase IV and the ligase cofactor XRCC4. The ATP-dependent ligation of free DNA ends is the final step in the NHEJ repair pathway (2). Research studies suggest that XLF and XRCC4 proteins form complexes that bridge DNA breaks earlier in the NHEJ pathway (3). Additional studies indicate that localization of XRCC4 to the nucleus and levels of XRCC4 protein are both regulated by DNA ligase IV (4). Mutations in the correspondingLIG4gene are associated with LIG4 syndrome, a disorder characterized by immunodeficiency and developmental growth delay. Cells isolated from patients diagnosed with LIG4 syndrome display typical cell cycle checkpoint activity, but aberrant rejoining of DNA double strand breaks (5,6).Hartlerode, A.J. and Scully, R. (2009)Biochem J423, 157-68.Tsai, C.J. et al. (2007)Proc Natl Acad Sci U S A104, 7851-6.Andres, S.N. et al. (2012)Nucleic Acids Res40, 1868-78.Francis, D.B. et al. (2014)DNA Repair (Amst)21, 36-42.O'Driscoll, M. et al. (2001)Mol Cell8, 1175-85.O'Driscoll, M. et al. (2004)DNA Repair (Amst)3, 1227-35.Alternate NamesDNA joinase; DNA ligase 4; DNA ligase IV; DNA repair enzyme; DNLI4; LIG4; LIG4S; ligase IV, DNA, ATP-dependent; Polydeoxyribonucleotide synthase [ATP] 4; polynucleotide ligase; sealase

DNA joinase; DNA ligase 4; DNA ligase IV; DNA repair enzyme; DNLI4; LIG4; LIG4S; ligase IV, DNA, ATP-dependent; Polydeoxyribonucleotide synthase [ATP] 4; polynucleotide ligase; sealase