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Gene Review

DNL4  -  DNA ligase (ATP) DNL4

Saccharomyces cerevisiae S288c

Synonyms: DNA ligase 4, DNA ligase II, DNA ligase IV, LIG4, UND407, ...
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High impact information on DNL4

  • Here we demonstrate that palindrome formation can occur in the absence of RAD50, YKU70, and LIG4, indicating that palindrome formation defines a new class of nonhomologous end joining events [1].
  • Disruption of LIF2 abolishes the capacity of cells to repair DSBs by end-joining to the same extent than lif1 and dnl4 mutants [2].
  • This DNA ligase shares significant amino acid sequence homology with human DNA ligase IV; accordingly, we designate the yeast gene LIG4 [3].
  • These telomere fusion events are DNL4 dependent [4].
  • Telomere fusions are not observed in cells lacking factors required for nonhomologous end joining (NHEJ), including Lig4 (ligase IV), KU and the Mre11 complex [5].

Biological context of DNL4

  • This novel temperature-sensitive phenotype is complemented by retransformation with a plasmid-borne DNL4 gene [6].
  • T-TFs require Lig4p (a ligase required for nonhomologous end-joining DNA repair) [7].
  • DNA double strand break (DSB) repair by non-homologous end joining (NHEJ) in mammalian cells requires the Ku70-Ku80 heterodimer, the DNA-PK catalytic subunit DNA-PKcs, as well as DNA ligase IV and Xrcc4 [8].
  • The deletion of the genes coding for Ku70 or DNA ligase IV, which are both obligatory constituents of the non-homologous end joining (NHEJ) pathway, each resulted in a 50% reduction of replication-independent mutation frequency in haploid cells [9].
  • The conclusion that nonhomologous end-joining is not required for chromosome circularization was further supported by analysis of survivors in strains lacking the genes for both trt1(+) and lig4(+) [10].

Anatomical context of DNL4


Associations of DNL4 with chemical compounds

  • The most striking observation, however, is that the DNA ligase II activity is not increased after dimethyl sulphate treatment as occurs in wild-type L1210 cells [12].

Other interactions of DNL4

  • This interaction stimulates the DNA synthesis activity of Pol4 and, to a lesser extent, the DNA joining activity of Dnl4-Lif1 [13].
  • Since this minor species does not appear to be a modified form of Cdc9 DNA ligase, it has been designated as S. cerevisiae DNA ligase II [14].

Analytical, diagnostic and therapeutic context of DNL4

  • For efficient NHEJ, NEJ1 is required as part of a complex with LIF1 and DNL4, which catalyzes DNA ligation [4].
  • Because nonhomologous integration is eliminated in a LIG4-disrupted strain, integration occurs only at the targeted site in mus-53 mutants, making them an extremely efficient and safe host for gene targeting [15].


  1. A mechanism of palindromic gene amplification in Saccharomyces cerevisiae. Rattray, A.J., Shafer, B.K., Neelam, B., Strathern, J.N. Genes Dev. (2005) [Pubmed]
  2. NHEJ regulation by mating type is exercised through a novel protein, Lif2p, essential to the ligase IV pathway. Frank-Vaillant, M., Marcand, S. Genes Dev. (2001) [Pubmed]
  3. A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks. Schär, P., Herrmann, G., Daly, G., Lindahl, T. Genes Dev. (1997) [Pubmed]
  4. NEJ1 prevents NHEJ-dependent telomere fusions in yeast without telomerase. Liti, G., Louis, E.J. Mol. Cell (2003) [Pubmed]
  5. Rap1 prevents telomere fusions by nonhomologous end joining. Pardo, B., Marcand, S. EMBO J. (2005) [Pubmed]
  6. Biochemical and genetic characterization of the DNA ligase encoded by Saccharomyces cerevisiae open reading frame YOR005c, a homolog of mammalian DNA ligase IV. Ramos, W., Liu, G., Giroux, C.N., Tomkinson, A.E. Nucleic Acids Res. (1998) [Pubmed]
  7. Genetic regulation of telomere-telomere fusions in the yeast Saccharomyces cerevisae. Mieczkowski, P.A., Mieczkowska, J.O., Dominska, M., Petes, T.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. Novel functional requirements for non-homologous DNA end joining in Schizosaccharomyces pombe. Manolis, K.G., Nimmo, E.R., Hartsuiker, E., Carr, A.M., Jeggo, P.A., Allshire, R.C. EMBO J. (2001) [Pubmed]
  9. Non-homologous end joining as an important mutagenic process in cell cycle-arrested cells. Heidenreich, E., Novotny, R., Kneidinger, B., Holzmann, V., Wintersberger, U. EMBO J. (2003) [Pubmed]
  10. Protection of telomeres by the Ku protein in fission yeast. Baumann, P., Cech, T.R. Mol. Biol. Cell (2000) [Pubmed]
  11. 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]
  12. A mammalian cell variant in which 3-aminobenzamide does not potentiate the cytotoxicity of dimethyl sulphate. Murray, B., Irwin, J., Creissen, D., Tavassoli, M., Durkacz, B.W., Shall, S. Mutat. Res. (1986) [Pubmed]
  13. A physical and functional interaction between yeast Pol4 and Dnl4-Lif1 links DNA synthesis and ligation in nonhomologous end joining. Tseng, H.M., Tomkinson, A.E. J. Biol. Chem. (2002) [Pubmed]
  14. Two distinct DNA ligase activities in mitotic extracts of the yeast Saccharomyces cerevisiae. Ramos, W., Tappe, N., Talamantez, J., Friedberg, E.C., Tomkinson, A.E. Nucleic Acids Res. (1997) [Pubmed]
  15. Nonhomologous chromosomal integration of foreign DNA is completely dependent on MUS-53 (human Lig4 homolog) in Neurospora. Ishibashi, K., Suzuki, K., Ando, Y., Takakura, C., Inoue, H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
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