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Gene Review

LIG3  -  ligase III, DNA, ATP-dependent

Homo sapiens

Synonyms: DNA ligase 3, DNA ligase III
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Disease relevance of LIG3


High impact information on LIG3

  • Furthermore, we demonstrate that the excision repair pathway of an abasic site can be reconstituted on core particles using the known repair enzymes, AP-endonuclease 1, DNA polymerase beta and DNA ligase III [6].
  • Furthermore, the established structure of an XRCC1 BRCT homodimer suggests potential protein-protein interaction sites for the complementary BRCT domain in DNA ligase III, since these two domains form a stable heterodimeric complex [7].
  • To determine its role in DNA repair, cellular growth, and embryonic development, we introduced targeted interruption of the DNA ligase III (LIG3) gene into the mouse [8].
  • This provides a mechanism for the recruitment of the DNA ligase IIIalpha-XRCC1 complex to in vivo DNA single-strand breaks and suggests that the zinc finger of DNA ligase III enables this complex and associated repair factors to locate the strand break in the presence of the negatively charged poly(ADP-ribose) polymer [9].
  • PARP-1 binds directly to an N-terminal region of DNA ligase III immediately adjacent to its zinc finger [9].

Biological context of LIG3


Anatomical context of LIG3

  • Interestingly, cell lines deficient in either DNA ligase I (46BR.1G1) or DNA ligase III (EM9) are sensitive to simple alkylating agents [10].
  • In contrast, DNA ligase III-beta, which does not interact with XRCC1, is only expressed in male meiotic germ cells, suggesting a role for this isoform in meiotic recombination [11].
  • We have recently purified DNA ligase II and DNA ligase III to near homogeneity from bovine liver and testis tissue, respectively [2].
  • In contrast, elevated levels of DNA ligase III mRNA were observed in primary spermatocytes undergoing recombination prior to the first meiotic division [2].
  • During male germ cell differentiation, elevated expression of DNA ligase III-beta mRNA is restricted, beginning only in the latter stages of meiotic prophase and ending in the round spermatid stage [13].

Associations of LIG3 with chemical compounds


Physical interactions of LIG3


Regulatory relationships of LIG3


Other interactions of LIG3


Analytical, diagnostic and therapeutic context of LIG3


  1. DNA repair gene XRCC1 polymorphisms in childhood acute lymphoblastic leukemia. Joseph, T., Kusumakumary, P., Chacko, P., Abraham, A., Pillai, M.R. Cancer Lett. (2005) [Pubmed]
  2. Mammalian DNA ligase III: molecular cloning, chromosomal localization, and expression in spermatocytes undergoing meiotic recombination. Chen, J., Tomkinson, A.E., Ramos, W., Mackey, Z.B., Danehower, S., Walter, C.A., Schultz, R.A., Besterman, J.M., Husain, I. Mol. Cell. Biol. (1995) [Pubmed]
  3. Specific function of DNA ligase I in simian virus 40 DNA replication by human cell-free extracts is mediated by the amino-terminal non-catalytic domain. Mackenney, V.J., Barnes, D.E., Lindahl, T. J. Biol. Chem. (1997) [Pubmed]
  4. DNA ligase III is degraded by calpain during cell death induced by DNA-damaging agents. Bordone, L., Campbell, C. J. Biol. Chem. (2002) [Pubmed]
  5. The CHO XRCC1 mutant, EM9, deficient in DNA ligase III activity, exhibits hypersensitivity to camptothecin independent of DNA replication. Barrows, L.R., Holden, J.A., Anderson, M., D'Arpa, P. Mutat. Res. (1998) [Pubmed]
  6. DNA base excision repair of uracil residues in reconstituted nucleosome core particles. Nilsen, H., Lindahl, T., Verreault, A. EMBO J. (2002) [Pubmed]
  7. Structure of an XRCC1 BRCT domain: a new protein-protein interaction module. Zhang, X., Moréra, S., Bates, P.A., Whitehead, P.C., Coffer, A.I., Hainbucher, K., Nash, R.A., Sternberg, M.J., Lindahl, T., Freemont, P.S. EMBO J. (1998) [Pubmed]
  8. Early Embryonic Lethality Due to Targeted Inactivation of DNA Ligase III. Puebla-Osorio, N., Lacey, D.B., Alt, F.W., Zhu, C. Mol. Cell. Biol. (2006) [Pubmed]
  9. Physical and functional interaction between DNA ligase IIIalpha and poly(ADP-Ribose) polymerase 1 in DNA single-strand break repair. Leppard, J.B., Dong, Z., Mackey, Z.B., Tomkinson, A.E. Mol. Cell. Biol. (2003) [Pubmed]
  10. Completion of base excision repair by mammalian DNA ligases. Tomkinson, A.E., Chen, L., Dong, Z., Leppard, J.B., Levin, D.S., Mackey, Z.B., Motycka, T.A. Prog. Nucleic Acid Res. Mol. Biol. (2001) [Pubmed]
  11. Mammalian DNA ligases. Tomkinson, A.E., Levin, D.S. Bioessays (1997) [Pubmed]
  12. Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1. Taylor, R.M., Wickstead, B., Cronin, S., Caldecott, K.W. Curr. Biol. (1998) [Pubmed]
  13. An alternative splicing event which occurs in mouse pachytene spermatocytes generates a form of DNA ligase III with distinct biochemical properties that may function in meiotic recombination. Mackey, Z.B., Ramos, W., Levin, D.S., Walter, C.A., McCarrey, J.R., Tomkinson, A.E. Mol. Cell. Biol. (1997) [Pubmed]
  14. An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III. Caldecott, K.W., McKeown, C.K., Tucker, J.D., Ljungquist, S., Thompson, L.H. Mol. Cell. Biol. (1994) [Pubmed]
  15. Mode of inhibition of short-patch base excision repair by thymine glycol within clustered DNA lesions. Budworth, H., Dianov, G.L. J. Biol. Chem. (2003) [Pubmed]
  16. A cell cycle-specific requirement for the XRCC1 BRCT II domain during mammalian DNA strand break repair. Taylor, R.M., Moore, D.J., Whitehouse, J., Johnson, P., Caldecott, K.W. Mol. Cell. Biol. (2000) [Pubmed]
  17. DNA ligase III is recruited to DNA strand breaks by a zinc finger motif homologous to that of poly(ADP-ribose) polymerase. Identification of two functionally distinct DNA binding regions within DNA ligase III. Mackey, Z.B., Niedergang, C., Murcia, J.M., Leppard, J., Au, K., Chen, J., de Murcia, G., Tomkinson, A.E. J. Biol. Chem. (1999) [Pubmed]
  18. Structure and function of mammalian DNA ligases. Tomkinson, A.E., Mackey, Z.B. Mutat. Res. (1998) [Pubmed]
  19. Characterization of the XRCC1-DNA ligase III complex in vitro and its absence from mutant hamster cells. Caldecott, K.W., Tucker, J.D., Stanker, L.H., Thompson, L.H. Nucleic Acids Res. (1995) [Pubmed]
  20. Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination. Wei, Y.F., Robins, P., Carter, K., Caldecott, K., Pappin, D.J., Yu, G.L., Wang, R.P., Shell, B.K., Nash, R.A., Schär, P. Mol. Cell. Biol. (1995) [Pubmed]
  21. Altered DNA ligase III activity in the CHO EM9 mutant. Ljungquist, S., Kenne, K., Olsson, L., Sandström, M. Mutat. Res. (1994) [Pubmed]
  22. The human DNA ligase III gene encodes nuclear and mitochondrial proteins. Lakshmipathy, U., Campbell, C. Mol. Cell. Biol. (1999) [Pubmed]
  23. Involvement of XRCC1 and DNA ligase III gene products in DNA base excision repair. Cappelli, E., Taylor, R., Cevasco, M., Abbondandolo, A., Caldecott, K., Frosina, G. J. Biol. Chem. (1997) [Pubmed]
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