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Gene Review

LIG1  -  ligase I, DNA, ATP-dependent

Homo sapiens

Synonyms: DNA ligase 1, DNA ligase I
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Disease relevance of LIG1


High impact information on LIG1

  • Mutational analysis and comparison of nick-bound structures of Rnl2 and human DNA ligase I highlight common and divergent themes of substrate recognition that can explain their specialization for RNA versus DNA repair [6].
  • Two missense mutations occurring in different alleles of the DNA ligase I gene, encoding the major DNA ligase in proliferating mammalian cells, were detected in a human fibroblast strain (46BR) [2].
  • Identification of the DNA ligase that mediates NHEJ in yeast will help elucidate the function of the four mammalian DNA ligases in DSBR, V(D)J recombination and other reactions [7].
  • Evidence is presented here, as in the accompanying paper from a different laboratory, for the existence in Bloom's syndrome of an abnormality of the DNA ligase involved in semi-conservative DNA replication [8].
  • Examination of the amino acid sequence of Nae I uncovered similarity to the active site of human DNA ligase I, except for leucine 43 in Nae I instead of the lysine essential for ligase activity [9].

Chemical compound and disease context of LIG1


Biological context of LIG1


Anatomical context of LIG1


Associations of LIG1 with chemical compounds

  • The substitution of serines at positions 51, 66, 76, and 91 with aspartic acid to mimic the phosphorylated enzyme hampers the association of DNA ligase I with the replication foci [24].
  • Finally, we demonstrate that DNA ligase III shares with poly (ADP-ribose) polymerase the novel function of a molecular DNA nick-sensor, and that the DNA ligase can inhibit activity of the latter polypeptide in vitro [25].
  • We show that wild type DNA ligase IV-Xrcc4 is an efficient double-stranded ligase with distinct optimal requirements for adenylate complex formation versus rejoining [26].
  • Complete DNA excision repair of pyrimidine dimers was achieved with the beta-polymerase, DNase V, and DNA ligase from incisions made in UV-irradiated DNA by T4 UV endonuclease and HeLa AP endonuclease II [27].
  • We subsequently demonstrated that the concerted reactions of polynucleotide kinase and purified human DNA ligase I could efficiently repair DNA nicks possessing 3'-phosphate and 5'-hydroxyl termini, and similarly the combination of these two enzymes together with purified rat DNA polymerase beta could seal a strand break with a 1 nt gap [28].

Physical interactions of LIG1

  • In addition, DNA ligase I participates in a second BER pathway that is carried out by a multiprotein complex in which DNA ligase I interacts directly with DNA polymerase beta [17].
  • XRCC1 not only forms a stable complex with DNA ligase IIIalpha but also interacts with several other DNA repair factors [29].
  • 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 [29].
  • The replication factory targeting sequence/PCNA-binding site is required in G(1) to control the phosphorylation status of DNA ligase I [30].

Enzymatic interactions of LIG1


Regulatory relationships of LIG1

  • We have investigated both DNA ligase activities and a protein which stimulates DNA ligase activity in mutant EM9 cells, XRCC1-transfectant H9T3-7-1 cells and wild-type AA8 cells [34].
  • Notably, the ability of DNA ligase I to promote the recombinational repair of DNA double-strand breaks was dependent upon its interaction with proliferating cell nuclear antigen [35].
  • Interestingly, treatment of S phase cells with agents that cause oxygen free radicals induces the dephosphorylation of DNA ligase IIIalpha [32].
  • DNA ligase I inhibited replication factor C-independent DNA synthesis by polymerase delta [36].

Other interactions of LIG1


Analytical, diagnostic and therapeutic context of LIG1


  1. Polymorphism of DNA ligase I and risk of lung cancer--a case-control analysis. Shen, H., Spitz, M.R., Qiao, Y., Zheng, Y., Hong, W.K., Wei, Q. Lung Cancer (2002) [Pubmed]
  2. Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents. Barnes, D.E., Tomkinson, A.E., Lehmann, A.R., Webster, A.D., Lindahl, T. Cell (1992) [Pubmed]
  3. Growth retardation and immunodeficiency in a patient with mutations in the DNA ligase I gene. Webster, A.D., Barnes, D.E., Arlett, C.F., Lehmann, A.R., Lindahl, T. Lancet (1992) [Pubmed]
  4. A wild-type DNA ligase I gene is expressed in Bloom's syndrome cells. Petrini, J.H., Huwiler, K.G., Weaver, D.T. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  5. 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]
  6. RNA Ligase Structures Reveal the Basis for RNA Specificity and Conformational Changes that Drive Ligation Forward. Nandakumar, J., Shuman, S., Lima, C.D. Cell (2006) [Pubmed]
  7. Yeast DNA ligase IV mediates non-homologous DNA end joining. Wilson, T.E., Grawunder, U., Lieber, M.R. Nature (1997) [Pubmed]
  8. Altered DNA ligase I activity in Bloom's syndrome cells. Chan, J.Y., Becker, F.F., German, J., Ray, J.H. Nature (1987) [Pubmed]
  9. DNA topoisomerase and recombinase activities in Nae I restriction endonuclease. Jo, K., Topal, M.D. Science (1995) [Pubmed]
  10. Enhanced repair of a cisplatin-damaged reporter chloramphenicol-O-acetyltransferase gene and altered activities of DNA polymerases alpha and beta, and DNA ligase in cells of a human malignant glioma following in vivo cisplatin therapy. Ali-Osman, F., Berger, M.S., Rairkar, A., Stein, D.E. J. Cell. Biochem. (1994) [Pubmed]
  11. Induction of DNA ligase I by 1-beta-D-arabinosylcytosine and aphidicolin in MiaPaCa human pancreatic cancer cells. Sun, D., Urrabaz, R., Buzello, C., Nguyen, M. Exp. Cell Res. (2002) [Pubmed]
  12. Concomitant reversion of the characteristic phenotypic properties of a cell line of Bloom's syndrome origin. Willis, A.E., Spurr, N.K., Lindahl, T. Carcinogenesis (1989) [Pubmed]
  13. Protection provided by exogenous DNA ligase in G0 human lymphocytes treated with restriction enzyme MspI or bleomycin as shown by the comet assay. Flores, M.J., Ortiz, T., Piñero, J., Cortés, F. Environ. Mol. Mutagen. (1998) [Pubmed]
  14. Phenotypic correction of a human cell line (46BR) with aberrant DNA ligase I activity. Somia, N.V., Jessop, J.K., Melton, D.W. Mutat. Res. (1993) [Pubmed]
  15. Chromosome 19q deletions in human gliomas overlap telomeric to D19S219 and may target a 425 kb region centromeric to D19S112. Yong, W.H., Chou, D., Ueki, K., Harsh, G.R., von Deimling, A., Gusella, J.F., Mohrenweiser, H.W., Louis, D.N. J. Neuropathol. Exp. Neurol. (1995) [Pubmed]
  16. Genetic mapping and expression analysis of the murine DNA ligase I gene. Gariboldi, M., Montecucco, A., Columbano, A., Ledda-Columbano, G.M., Savini, E., Manenti, G., Pierotti, M.A., Dragani, T.A. Mol. Carcinog. (1995) [Pubmed]
  17. Structure and function of mammalian DNA ligases. Tomkinson, A.E., Mackey, Z.B. Mutat. Res. (1998) [Pubmed]
  18. Differential recruitment of DNA Ligase I and III to DNA repair sites. Mortusewicz, O., Rothbauer, U., Cardoso, M.C., Leonhardt, H. Nucleic Acids Res. (2006) [Pubmed]
  19. 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]
  20. Assignment of the gene encoding DNA ligase I to human chromosome 19q13.2-13.3. Barnes, D.E., Kodama, K., Tynan, K., Trask, B.J., Christensen, M., De Jong, P.J., Spurr, N.K., Lindahl, T., Mohrenweiser, H.W. Genomics (1992) [Pubmed]
  21. 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]
  22. Base excision repair is limited by different proteins in male germ cell nuclear extracts prepared from young and old mice. Intano, G.W., McMahan, C.A., McCarrey, J.R., Walter, R.B., McKenna, A.E., Matsumoto, Y., MacInnes, M.A., Chen, D.J., Walter, C.A. Mol. Cell. Biol. (2002) [Pubmed]
  23. Mammalian DNA ligases. Biosynthesis and intracellular localization of DNA ligase I. Lasko, D.D., Tomkinson, A.E., Lindahl, T. J. Biol. Chem. (1990) [Pubmed]
  24. Cell cycle-dependent phosphorylation of human DNA ligase I at the cyclin-dependent kinase sites. Ferrari, G., Rossi, R., Arosio, D., Vindigni, A., Biamonti, G., Montecucco, A. J. Biol. Chem. (2003) [Pubmed]
  25. XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular 'nick-sensor' in vitro. Caldecott, K.W., Aoufouchi, S., Johnson, P., Shall, S. Nucleic Acids Res. (1996) [Pubmed]
  26. Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity. Riballo, E., Doherty, A.J., Dai, Y., Stiff, T., Oettinger, M.A., Jeggo, P.A., Kysela, B. J. Biol. Chem. (2001) [Pubmed]
  27. Excision repair and DNA synthesis with a combination of HeLa DNA polymerase beta and DNase V. Mosbaugh, D.W., Linn, S. J. Biol. Chem. (1983) [Pubmed]
  28. Repair of DNA strand gaps and nicks containing 3'-phosphate and 5'-hydroxyl termini by purified mammalian enzymes. Karimi-Busheri, F., Lee, J., Tomkinson, A.E., Weinfeld, M. Nucleic Acids Res. (1998) [Pubmed]
  29. 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]
  30. The replication factory targeting sequence/PCNA-binding site is required in G(1) to control the phosphorylation status of DNA ligase I. Rossi, R., Villa, A., Negri, C., Scovassi, I., Ciarrocchi, G., Biamonti, G., Montecucco, A. EMBO J. (1999) [Pubmed]
  31. DNA ligase I competes with FEN1 to expand repetitive DNA sequences in vitro. Henricksen, L.A., Veeraraghavan, J., Chafin, D.R., Bambara, R.A. J. Biol. Chem. (2002) [Pubmed]
  32. ATM mediates oxidative stress-induced dephosphorylation of DNA ligase III{alpha}. Dong, Z., Tomkinson, A.E. Nucleic Acids Res. (2006) [Pubmed]
  33. Modulation of the 5'-deoxyribose-5-phosphate lyase and DNA synthesis activities of mammalian DNA polymerase beta by apurinic/apyrimidinic endonuclease 1. Wong, D., Demple, B. J. Biol. Chem. (2004) [Pubmed]
  34. Altered DNA ligase III activity in the CHO EM9 mutant. Ljungquist, S., Kenne, K., Olsson, L., Sandström, M. Mutat. Res. (1994) [Pubmed]
  35. Reduced repair of DNA double-strand breaks by homologous recombination in a DNA ligase I-deficient human cell line. Goetz, J.D., Motycka, T.A., Han, M., Jasin, M., Tomkinson, A.E. DNA Repair (Amst.) (2005) [Pubmed]
  36. DNA ligase I selectively affects DNA synthesis by DNA polymerases delta and epsilon suggesting differential functions in DNA replication and repair. Mossi, R., Ferrari, E., Hübscher, U. J. Biol. Chem. (1998) [Pubmed]
  37. AP endonuclease 1 coordinates flap endonuclease 1 and DNA ligase I activity in long patch base excision repair. Ranalli, T.A., Tom, S., Bambara, R.A. J. Biol. Chem. (2002) [Pubmed]
  38. The human checkpoint sensor and alternative DNA clamp Rad9-Rad1-Hus1 modulates the activity of DNA ligase I, a component of the long-patch base excision repair machinery. Smirnova, E., Toueille, M., Markkanen, E., Hübscher, U. Biochem. J. (2005) [Pubmed]
  39. Determination of human DNA polymerase utilization for the repair of a model ionizing radiation-induced DNA strand break lesion in a defined vector substrate. Winters, T.A., Russell, P.S., Kohli, M., Dar, M.E., Neumann, R.D., Jorgensen, T.J. Nucleic Acids Res. (1999) [Pubmed]
  40. Analysis of human flap endonuclease 1 mutants reveals a mechanism to prevent triplet repeat expansion. Liu, Y., Bambara, R.A. J. Biol. Chem. (2003) [Pubmed]
  41. Thermodynamics of human DNA ligase I trimerization and association with DNA polymerase beta. Dimitriadis, E.K., Prasad, R., Vaske, M.K., Chen, L., Tomkinson, A.E., Lewis, M.S., Wilson, S.H. J. Biol. Chem. (1998) [Pubmed]
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