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Gene Review

Lig4  -  ligase IV, DNA, ATP-dependent

Mus musculus

Synonyms: 5830471N16Rik, DNA ligase 4, DNA ligase IV, tiny
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Disease relevance of Lig4


High impact information on Lig4


Biological context of Lig4


Anatomical context of Lig4

  • DNA ligase IV is the most recently identified member of a family of enzymes joining DNA strand breaks in mammalian cell nuclei [1] [2] [12].

Associations of Lig4 with chemical compounds


Physical interactions of Lig4

  • The C-terminal stalk comprising a single alpha-helix >120 A in length is partly incorporated into a four-helix bundle in the Xrcc4 tetramer and partly involved in interacting with ligase IV [14].

Other interactions of Lig4

  • DNA ligase IV (Lig4) and the DNA-dependent protein kinase (DNA-PK) function in nonhomologous end joining (NHEJ) [8].
  • The Xrcc4 structure suggests a possible mode of coupling ligase IV association with DNA binding for effective ligation of DNA ends [14].
  • DNA damage-induced apoptosis resulting from inactivation of HR (Xrcc2 deficiency) only occurred in proliferating neural precursor cells, whereas disruption of NHEJ (DNA ligase IV deficiency) mainly affected differentiating cells at later developmental stages [15].
  • Ku86 and DNA ligase IV are two major proteins in the NHEJ pathway [16].
  • Because mice with combined disruptions of ATM and other NHEJ components (ligase IV, Artemis) are viable, our data suggest a novel NHEJ-independent function for Prkdc/Ku that is required to complete early embryogenesis in the absence of ATM [17].


  1. DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway. Frank, K.M., Sharpless, N.E., Gao, Y., Sekiguchi, J.M., Ferguson, D.O., Zhu, C., Manis, J.P., Horner, J., DePinho, R.A., Alt, F.W. Mol. Cell (2000) [Pubmed]
  2. DNA ligase IV suppresses medulloblastoma formation. Lee, Y., McKinnon, P.J. Cancer Res. (2002) [Pubmed]
  3. Evidence that stable retroviral transduction and cell survival following DNA integration depend on components of the nonhomologous end joining repair pathway. Daniel, R., Greger, J.G., Katz, R.A., Taganov, K.D., Wu, X., Kappes, J.C., Skalka, A.M. J. Virol. (2004) [Pubmed]
  4. Late embryonic lethality and impaired V(D)J recombination in mice lacking DNA ligase IV. Frank, K.M., Sekiguchi, J.M., Seidl, K.J., Swat, W., Rathbun, G.A., Cheng, H.L., Davidson, L., Kangaloo, L., Alt, F.W. Nature (1998) [Pubmed]
  5. Rad54 and DNA Ligase IV cooperate to maintain mammalian chromatid stability. Mills, K.D., Ferguson, D.O., Essers, J., Eckersdorff, M., Kanaar, R., Alt, F.W. Genes Dev. (2004) [Pubmed]
  6. Defective neurogenesis resulting from DNA ligase IV deficiency requires Atm. Lee, Y., Barnes, D.E., Lindahl, T., McKinnon, P.J. Genes Dev. (2000) [Pubmed]
  7. A biochemically defined system for mammalian nonhomologous DNA end joining. Ma, Y., Lu, H., Tippin, B., Goodman, M.F., Shimazaki, N., Koiwai, O., Hsieh, C.L., Schwarz, K., Lieber, M.R. Mol. Cell (2004) [Pubmed]
  8. Genetic interactions between ATM and the nonhomologous end-joining factors in genomic stability and development. Sekiguchi, J., Ferguson, D.O., Chen, H.T., Yang, E.M., Earle, J., Frank, K., Whitlow, S., Gu, Y., Xu, Y., Nussenzweig, A., Alt, F.W. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  9. Defective embryonic neurogenesis in Ku-deficient but not DNA-dependent protein kinase catalytic subunit-deficient mice. Gu, Y., Sekiguchi, J., Gao, Y., Dikkes, P., Frank, K., Ferguson, D., Hasty, P., Chun, J., Alt, F.W. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  10. The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations. Ferguson, D.O., Sekiguchi, J.M., Chang, S., Frank, K.M., Gao, Y., DePinho, R.A., Alt, F.W. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  11. DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Celli, G.B., de Lange, T. Nat. Cell Biol. (2005) [Pubmed]
  12. Targeted disruption of the gene encoding DNA ligase IV leads to lethality in embryonic mice. Barnes, D.E., Stamp, G., Rosewell, I., Denzel, A., Lindahl, T. Curr. Biol. (1998) [Pubmed]
  13. Identification of a mutated DNA ligase IV gene in the X-ray-hypersensitive mutant SX10 of mouse FM3A cells. Sado, K., Ayusawa, D., Enomoto, A., Suganuma, T., Oshimura, M., Sato, K., Koyama, H. J. Biol. Chem. (2001) [Pubmed]
  14. Crystal structure of the Xrcc4 DNA repair protein and implications for end joining. Junop, M.S., Modesti, M., Guarné, A., Ghirlando, R., Gellert, M., Yang, W. EMBO J. (2000) [Pubmed]
  15. Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development. Orii, K.E., Lee, Y., Kondo, N., McKinnon, P.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  16. The nonhomologous DNA end joining pathway is important for chromosome stability in primary fibroblasts. Karanjawala, Z.E., Grawunder, U., Hsieh, C.L., Lieber, M.R. Curr. Biol. (1999) [Pubmed]
  17. p53-Independent apoptosis disrupts early organogenesis in embryos lacking both ataxia-telangiectasia mutated and Prkdc. Gladdy, R.A., Nutter, L.M., Kunath, T., Danska, J.S., Guidos, C.J. Mol. Cancer Res. (2006) [Pubmed]
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