Gene Symbol: LIG3
Description: DNA ligase 3
Alias: LIG2, DNA ligase 3, ligase II, DNA, ATP-dependent, ligase III, DNA, ATP-dependent, polydeoxyribonucleotide synthase [ATP] 3
Species: human
Products:     LIG3

Top Publications

  1. Leppard J, Dong Z, Mackey Z, Tomkinson A. Physical and functional interaction between DNA ligase IIIalpha and poly(ADP-Ribose) polymerase 1 in DNA single-strand break repair. Mol Cell Biol. 2003;23:5919-27 pubmed
  2. Caldecott K, McKeown C, Tucker J, Ljungquist S, Thompson L. An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III. Mol Cell Biol. 1994;14:68-76 pubmed
    ..These findings indicate that XRCC1 is required for normal levels of DNA ligase III activity, and they implicate a major role for this DNA ligase in DNA base excision repair in mammalian cells. ..
  3. Caldecott K, Tucker J, Stanker L, Thompson L. Characterization of the XRCC1-DNA ligase III complex in vitro and its absence from mutant hamster cells. Nucleic Acids Res. 1995;23:4836-43 pubmed
    ..Immunodetection of XRCC1 on Western blots revealed that the level of this polypeptide was also decreased in EM9 and EM-C11 (> 10-fold), indicating that the XRCC1-DNA ligase III complex is much reduced in the two CHO mutants. ..
  4. Kubota Y, Nash R, Klungland A, Schär P, Barnes D, Lindahl T. Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. EMBO J. 1996;15:6662-70 pubmed
    ..DNA strand displacement and excessive gap filling during DNA repair were observed in cell-free extracts of an XRCC1-deficient mutant cell line, in agreement with the results from the reconstituted system. ..
  5. Nash R, Caldecott K, Barnes D, Lindahl T. XRCC1 protein interacts with one of two distinct forms of DNA ligase III. Biochemistry. 1997;36:5207-11 pubmed
    ..These findings indicate that only the larger form of DNA ligase III acts together with XRCC1, suggesting a role for this isoform of the enzyme in base excision repair. ..
  6. De A, Campbell C. A novel interaction between DNA ligase III and DNA polymerase gamma plays an essential role in mitochondrial DNA stability. Biochem J. 2007;402:175-86 pubmed
    ..These data support the interpretation that the interaction of DNA ligase III and DNA polymerase gamma is required for proper maintenance of the mammalian mitochondrial genome. ..
  7. Chen X, Ballin J, Della Maria J, Tsai M, White E, Tomkinson A, et al. Distinct kinetics of human DNA ligases I, IIIalpha, IIIbeta, and IV reveal direct DNA sensing ability and differential physiological functions in DNA repair. DNA Repair (Amst). 2009;8:961-8 pubmed publisher
  8. Lakshmipathy U, Campbell C. The human DNA ligase III gene encodes nuclear and mitochondrial proteins. Mol Cell Biol. 1999;19:3869-76 pubmed
    ..DNA ligase plays a central role in DNA replication, recombination, and DNA repair. Thus, identification of a mitochondrial form of this enzyme provides a tool with which to dissect mammalian mitochondrial genome dynamics. ..
  9. Cotner Gohara E, Kim I, Tomkinson A, Ellenberger T. Two DNA-binding and nick recognition modules in human DNA ligase III. J Biol Chem. 2008;283:10764-72 pubmed publisher
    ..We present a jackknife model for ligase III that posits conformational changes during nick sensing and ligation to extend the versatility of the enzyme. ..

More Information


  1. Mackey Z, Ramos W, Levin D, Walter C, McCarrey J, Tomkinson A. 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. Mol Cell Biol. 1997;17:989-98 pubmed
  2. Moser J, Kool H, Giakzidis I, Caldecott K, Mullenders L, Fousteri M. Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase III alpha in a cell-cycle-specific manner. Mol Cell. 2007;27:311-23 pubmed
    ..XRCC1-DNA ligase IIIalpha (XRCC1-Lig3) plays a central role in the repair of DNA single-strand breaks but has never been implicated in NER...
  3. Simsek D, Furda A, Gao Y, Artus J, Brunet E, Hadjantonakis A, et al. Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair. Nature. 2011;471:245-8 pubmed publisher
    ..Homologues of ligase I (Lig1) and ligase IV (Lig4) are ubiquitous in Eukarya, whereas ligase III (Lig3), which has nuclear and mitochondrial forms, appears to be restricted to vertebrates...
  4. Wei Y, Robins P, Carter K, Caldecott K, Pappin D, Yu G, et al. 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. Mol Cell Biol. 1995;15:3206-16 pubmed
    ..DNA ligases III and IV are encoded by distinct genes located on human chromosomes 17q11.2-12 and 13q33-34, respectively. ..
  5. Whitehouse C, Taylor R, Thistlethwaite A, Zhang H, Karimi Busheri F, Lasko D, et al. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell. 2001;104:107-17 pubmed
    ..These data identify a novel pathway for mammalian single-strand break repair and demonstrate a concerted role for XRCC1 and PNK in the initial step of processing damaged DNA ends. ..
  6. Kwiatkowski D, Czarny P, Toma M, Korycińska A, Sowinska K, Galecki P, et al. Association between Single-Nucleotide Polymorphisms of the hOGG1,NEIL1,APEX1, FEN1,LIG1, and LIG3 Genes and Alzheimer's Disease Risk. Neuropsychobiology. 2016;73:98-107 pubmed publisher
    ..We analyzed the following SNP: c.-468T>G and c.444T>G of APEX1, c.*50C>T and c.*83A>C of LIG3, c.977C>G of OGG1, c.*283C>G of NEIL1, c.-441G>A of FEN1, and c.-7C>T of LIG1...
  7. Abdou I, Poirier G, Hendzel M, Weinfeld M. DNA ligase III acts as a DNA strand break sensor in the cellular orchestration of DNA strand break repair. Nucleic Acids Res. 2015;43:875-92 pubmed publisher
    ..However, biochemical studies have implicated LIG3 as another possible SSB sensor...
  8. Iida R, Ueki M, Yasuda T. Knockout of Mpv17-Like Protein (M-LPH) Gene in Human Hepatoma Cells Results in Impairment of mtDNA Integrity through Reduction of TFAM, OGG1, and LIG3 at the Protein Levels. Oxid Med Cell Longev. 2018;2018:6956414 pubmed publisher
    ..for transcription and maintenance of mtDNA, and two DNA repair enzymes, 8-oxoguanine DNA glycosylase (OGG1) and DNA ligase 3 (LIG3), both involved in mitochondrial base excision repair (BER)...
  9. Li G, Wang X, Wang X, Guan Z, Guo J, Wang F, et al. Polymorphism rs1052536 in Base Excision Repair Gene Is a Risk Factor in a High-Risk Area of Neural Tube Defects in China. Med Sci Monit. 2018;24:5015-5026 pubmed publisher
    BACKGROUND DNA Base Excision Repair Gene-DNA LigaseIII (LIG3) is an important repair gene in the repair pathway and plays an important role in maintaining the integrity of mitochondria...
  10. Thornton K, Krishnan V, West M, Popham J, Ramirez M, Thelen M, et al. Expression, purification, and biophysical characterization of the BRCT domain of human DNA ligase IIIalpha. Protein Expr Purif. 2001;21:401-11 pubmed
    ..This increased thermostability imparted by the interaction between the two BRCT domains may explain why cells require XRCC1 to maintain ligase IIIalpha activity. ..
  11. Soni A, Siemann M, Pantelias G, Iliakis G. Marked contribution of alternative end-joining to chromosome-translocation-formation by stochastically induced DNA double-strand-breaks in G2-phase human cells. Mutat Res Genet Toxicol Environ Mutagen. 2015;793:2-8 pubmed publisher demonstrated by a yield-reduction after treatment with inhibitors of Parp, or of DNA ligases 1 and 3 (Lig1, Lig3)...
  12. Newman E, Lu F, Bashllari D, Wang L, Opipari A, Castle V. Alternative NHEJ Pathway Components Are Therapeutic Targets in High-Risk Neuroblastoma. Mol Cancer Res. 2015;13:470-82 pubmed publisher
    ..Conversely, enzymes required for an error-prone alternative NHEJ pathway (alt-NHEJ), DNA Ligase IIIα (Lig3), DNA Ligase I (Lig1), and PARP1 protein were upregulated...
  13. Arakawa H, Iliakis G. Alternative Okazaki Fragment Ligation Pathway by DNA Ligase III. Genes (Basel). 2015;6:385-98 pubmed publisher
    Higher eukaryotes have three types of DNA ligases: DNA ligase 1 (Lig1), DNA ligase 3 (Lig3) and DNA ligase 4 (Lig4)...
  14. Van Houten B, Hunter S, Meyer J. Mitochondrial DNA damage induced autophagy, cell death, and disease. Front Biosci (Landmark Ed). 2016;21:42-54 pubmed
    ..However, accumulation of certain types of mitochondrial damage, in the absence of DNA ligase III (Lig3) or exonuclease G (EXOG), can directly trigger cell death...
  15. De Langhe S, Mulliez T, Veldeman L, Remouchamps V, Van Greveling A, Gilsoul M, et al. Factors modifying the risk for developing acute skin toxicity after whole-breast intensity modulated radiotherapy. BMC Cancer. 2014;14:711 pubmed publisher
    ..Patient- and treatment-related factors and genetic markers in regulatory regions of radioresponsive genes and in LIG3, MLH1 and XRCC3 genes were considered as variables. Acute dermatitis was scored using the CTCAEv3.0 scoring system...
  16. Hu Y, Lin J, Fang H, Fang J, Li C, Chen W, et al. Targeting the MALAT1/PARP1/LIG3 complex induces DNA damage and apoptosis in multiple myeloma. Leukemia. 2018;32:2250-2262 pubmed publisher
    ..elevated MALAT1 and involve in alternative non-homozygous end joining (A-NHEJ) pathway by binding to PARP1 and LIG3, two key components of the A-NHEJ protein complex...
  17. Caracciolo D, Di Martino M, Amodio N, Morelli E, Montesano M, Botta C, et al. miR-22 suppresses DNA ligase III addiction in multiple myeloma. Leukemia. 2019;33:487-498 pubmed publisher
    ..Here we provide evidence that hyper-activation of DNA ligase III (LIG3) is crucial for genomic instability and survival of MM cells...
  18. Badie S, Carlos A, Folio C, Okamoto K, Bouwman P, Jonkers J, et al. BRCA1 and CtIP promote alternative non-homologous end-joining at uncapped telomeres. EMBO J. 2015;34:410-24 pubmed publisher
    ..dependent on Ku70/80 and LIG4, or the alternative non-homologous end-joining (A-NHEJ), which relies on PARP1 and LIG3. Here, we show that the tumour suppressor BRCA1, together with its interacting partner CtIP, both acting in end ..
  19. Kang Y, Yan C. Regulation of DNA repair in the absence of classical non-homologous end joining. DNA Repair (Amst). 2018;68:34-40 pubmed publisher
    ..These include components of base-excision repair (PARP1/XRCC1/LIG3), interstrand cross-link repair (BRCA1/FANCD2), and DSB response/DNA end-resection (MRE11A/RAD50/RBBP8)...
  20. Pashaiefar H, Yaghmaie M, Tavakkoly Bazzaz J, Hamidollah Ghaffari S, Alimoghaddam K, Izadi P, et al. The Association between PARP1 and LIG3 Expression Levels and Chromosomal Translocations in Acute Myeloid Leukemia Patients. Cell J. 2018;20:204-210 pubmed publisher
    ..Here, we examined the expression levels of the main components of alt-NHEJ (PARP1 and LIG3) in acute myeloid leukemia (AML) patients and assessed their potential correlation with the formation of ..
  21. Szefler B, Diudea M, Putz M, Grudziński I. Molecular Dynamic Studies of the Complex Polyethylenimine and Glucose Oxidase. Int J Mol Sci. 2016;17: pubmed
    ..8 kcal/mol and (LIG2) of -4.5 kcal/mol located inside the enzyme and on its surface, respectively...
  22. Grindel A, Guggenberger B, Eichberger L, Pöppelmeyer C, Gschaider M, Tosevska A, et al. Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2. PLoS ONE. 2016;11:e0162082 pubmed publisher
    ..5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with >7.5% HbA1c...
  23. Jensen H, Lillenes M, Rabano A, Günther C, Riaz T, Kalayou S, et al. Expression of nucleotide excision repair in Alzheimer's disease is higher in brain tissue than in blood. Neurosci Lett. 2018;672:53-58 pubmed publisher
    ..The mRNA levels of the genes encoding the NER proteins RAD23B, RPA1, ERCC1, PCNA and LIG3 as well as the NER-interacting base excision repair protein MPG in blood and brain tissue from four brain regions ..
  24. Spadafora D, Kozhukhar N, Alexeyev M. Presequence-Independent Mitochondrial Import of DNA Ligase Facilitates Establishment of Cell Lines with Reduced mtDNA Copy Number. PLoS ONE. 2016;11:e0152705 pubmed publisher
    ..first, transducing them with a retrovirus encoding LigA, and then inactivating in these transductants endogenous Lig3 with CRISPR-Cas9...
  25. Czarny P, Kwiatkowski D, Toma M, Kubiak J, Sliwinska A, Talarowska M, et al. Impact of Single Nucleotide Polymorphisms of Base Excision Repair Genes on DNA Damage and Efficiency of DNA Repair in Recurrent Depression Disorder. Mol Neurobiol. 2017;54:4150-4159 pubmed publisher
    ..2285T>C-PARP1, c.580C>T-XRCC1, c.1196A>G-XRCC1, c.444T>G-APEX1, c.-468T>G-APEX1, or c.*50C>T-LIG3. Our study suggests that both oxidative stress and disorders in DNA damage repair mechanisms contribute to elevated ..
  26. Czarny P, Kwiatkowski D, Toma M, Gałecki P, Orzechowska A, Bobinska K, et al. Single-Nucleotide Polymorphisms of Genes Involved in Repair of Oxidative DNA Damage and the Risk of Recurrent Depressive Disorder. Med Sci Monit. 2016;22:4455-4474 pubmed
    ..580C>T (rs1799782) and c.1196A>G (rs25487) of XRCC1, c.*83A>C (rs4796030) and c.*50C>T (rs1052536) of LIG3, c.-7C>T (rs20579) of LIG1, and c.-468T>G (rs1760944) and c...
  27. Iida R, Ueki M, Yasuda T. Identification of interacting partners of Human Mpv17-like protein with a mitigating effect of mitochondrial dysfunction through mtDNA damage. Free Radic Biol Med. 2015;87:336-45 pubmed publisher
    ..M-LPH foci, and these foci were co-localized with two enzymes, DNA polymerase γ (POLG) and DNA ligase III (LIG3), both involved in mtDNA repair...
  28. Paul Konietzko K, Thomale J, Arakawa H, Iliakis G. DNA Ligases I and III Support Nucleotide Excision Repair in DT40 Cells with Similar Efficiency. Photochem Photobiol. 2015;91:1173-80 pubmed publisher
    ..Lig1 has been implicated as the major DNA ligase in NER. Recently, Lig3 has been implicated as a component of a NER subpathway that operates in dividing cells, but which becomes ..
  29. Lu G, Duan J, Shu S, Wang X, Gao L, Guo J, et al. Ligase I and ligase III mediate the DNA double-strand break ligation in alternative end-joining. Proc Natl Acad Sci U S A. 2016;113:1256-60 pubmed publisher
    ..protein 9 (Cas9) system, we generated mouse CH12F3 cell lines in which, in addition to Lig4, either Lig1 or nuclear Lig3, representing the cells containing a single DNA ligase (Lig3 or Lig1, respectively) in their nucleus, was ..
  30. Sharma N, Lebedeva M, Thomas T, Kovalenko O, Stumpf J, Shadel G, et al. Intrinsic mitochondrial DNA repair defects in Ataxia Telangiectasia. DNA Repair (Amst). 2014;13:22-31 pubmed publisher
    ..of mtDNA repair proteins are essentially normal, in the absence of ATM levels specifically of DNA ligase III (Lig3), the only DNA ligase working in mitochondria is reduced...
  31. Masani S, Han L, Meek K, Yu K. Redundant function of DNA ligase 1 and 3 in alternative end-joining during immunoglobulin class switch recombination. Proc Natl Acad Sci U S A. 2016;113:1261-6 pubmed publisher
    ..that CSR levels are not further reduced by deletion of either of the two remaining DNA ligases (Lig1 and nuclear Lig3) in Lig4(-/-) cells...
  32. Chatterjee N, Lin Y, Yotnda P, Wilson J. Environmental Stress Induces Trinucleotide Repeat Mutagenesis in Human Cells by Alt-Nonhomologous End Joining Repair. J Mol Biol. 2016;428:2978-80 pubmed publisher
    ..We now show that knockdown of alt-nonhomologous end joining (alt-NHEJ) components-XRCC1, LIG3, and PARP1-suppresses stress-induced TNR mutagenesis, in contrast to the components of homologous recombination and ..
  33. Elia A, Wang D, Willis N, Boardman A, Hajdu I, Adeyemi R, et al. RFWD3-Dependent Ubiquitination of RPA Regulates Repair at Stalled Replication Forks. Mol Cell. 2015;60:280-93 pubmed publisher
    ..Multisite protein group sumoylation is known to promote HR in yeast. Our findings reveal a similar requirement for multisite protein group ubiquitination during HR at stalled forks in mammalian cells. ..
  34. Kukshal V, Kim I, Hura G, Tomkinson A, Tainer J, Ellenberger T. Human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining. Nucleic Acids Res. 2015;43:7021-31 pubmed publisher
    ..In contrast, these domains collaborate and are essential for formation of a DNA-bridging intermediate by adenylated LigIII that positions a pair of blunt-ended duplex DNAs for efficient and specific intermolecular ligation. ..
  35. Synowiec E, Wojcik K, Izdebska J, Binczyk E, Szaflik J, Blasiak J, et al. Polymorphism of the LIG3 gene in keratoconus and Fuchs endothelial corneal dystrophy. Cell Mol Biol (Noisy-le-grand). 2015;61:56-63 pubmed
    The product of the LIG3 gene encodes DNA ligase III, which is involved in the repair of oxidatively damaged DNA in the base excision repair pathway...
  36. Chen J, Tomkinson A, Ramos W, Mackey Z, Danehower S, Walter C, et al. Mammalian DNA ligase III: molecular cloning, chromosomal localization, and expression in spermatocytes undergoing meiotic recombination. Mol Cell Biol. 1995;15:5412-22 pubmed
    ..Therefore, we suggest that DNA ligase III seals DNA strand breaks that arise during the process of meiotic recombination in germ cells and as a consequence of DNA damage in somatic cells. ..
  37. Oh S, Harvey A, Zimbric J, Wang Y, Nguyen T, Jackson P, et al. DNA ligase III and DNA ligase IV carry out genetically distinct forms of end joining in human somatic cells. DNA Repair (Amst). 2014;21:97-110 pubmed publisher
    ..Moreover, we describe that a robust Ku-independent, LIGIV-dependent repair pathway exists in human somatic cells. ..
  38. El Khamisy S, Saifi G, Weinfeld M, Johansson F, Helleday T, Lupski J, et al. Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1. Nature. 2005;434:108-13 pubmed
    ..These data identify a defect in SSBR in a neurodegenerative disease, and implicate this process in the maintenance of genetic integrity in post-mitotic neurons. ..
  39. Falck J, Coates J, Jackson S. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature. 2005;434:605-11 pubmed
  40. Zhang Y, Newcomb P, Egan K, Titus Ernstoff L, Chanock S, Welch R, et al. Genetic polymorphisms in base-excision repair pathway genes and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2006;15:353-8 pubmed
    ..We evaluated whether genetic variation in six BER pathway genes (XRCC1, ADPRT, APEX1, OGG1, LIG3, and MUTYH) is associated with breast cancer risk in two large population-based case-control studies in the United ..
  41. Bordone L, Campbell C. DNA ligase III is degraded by calpain during cell death induced by DNA-damaging agents. J Biol Chem. 2002;277:26673-80 pubmed
    ..These data show that calpain-mediated proteolysis of DNA ligase III plays an essential role in DNA damage-induced cell death in human cells. ..
  42. Chiang S, Carroll J, El Khamisy S. TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage. Cell Cycle. 2010;9:588-595 pubmed
    ..Together, our findings highlight a novel mechanism for regulating TDP1 function in mammalian cells that is not directly related to its enzymatic activity. ..
  43. Newton Cheh C, Eijgelsheim M, Rice K, de Bakker P, Yin X, Estrada K, et al. Common variants at ten loci influence QT interval duration in the QTGEN Study. Nat Genet. 2009;41:399-406 pubmed publisher
    ..loci, including 16q21 near NDRG4 and GINS3, 6q22 near PLN, 1p36 near RNF207, 16p13 near LITAF and 17q12 near LIG3 and RFFL. Collectively, the 14 independent variants at these 10 loci explain 5.4-6...
  44. Della Maria J, Zhou Y, Tsai M, Kuhnlein J, Carney J, Paull T, et al. Human Mre11/human Rad50/Nbs1 and DNA ligase IIIalpha/XRCC1 protein complexes act together in an alternative nonhomologous end joining pathway. J Biol Chem. 2011;286:33845-53 pubmed publisher
    ..Thus, our results provide novel mechanistic insights into the alt-NHEJ pathway that not only contributes to genome instability in cancer cells but may also be a therapeutic target. ..
  45. Tomkinson A, Levin D. Mammalian DNA ligases. Bioessays. 1997;19:893-901 pubmed
    ..Three mammalian genes encoding DNA ligases, LIG1, LIG3 and LIG4, have been identified...
  46. Petermann E, Keil C, Oei S. Roles of DNA ligase III and XRCC1 in regulating the switch between short patch and long patch BER. DNA Repair (Amst). 2006;5:544-55 pubmed
    ..Accordingly, lowering the levels of the XRCC1/Lig III complex in HeLa cells using siRNA decreases ligation capacity but enhances Pol beta-dependent DNA synthesis. ..
  47. Heale J, Ball A, Schmiesing J, Kim J, Kong X, Zhou S, et al. Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair. Mol Cell. 2006;21:837-48 pubmed
    ..Furthermore, depletion of condensin in vivo compromises SSB but not double-strand break (DSB) repair. Our results identify a SSB-specific response of condensin I through PARP-1 and demonstrate a role for condensin in SSB repair. ..
  48. Landi S, Gemignani F, Canzian F, Gaborieau V, Barale R, Landi D, et al. DNA repair and cell cycle control genes and the risk of young-onset lung cancer. Cancer Res. 2006;66:11062-9 pubmed DNA damage sensing (ATM) and, interestingly, in four genes encoding proteins involved in mismatch repair (LIG1, LIG3, MLH1, and MSH6)...
  49. Jeyakumar M, Liu X, Erdjument Bromage H, Tempst P, Bagchi M. Phosphorylation of thyroid hormone receptor-associated nuclear receptor corepressor holocomplex by the DNA-dependent protein kinase enhances its histone deacetylase activity. J Biol Chem. 2007;282:9312-22 pubmed
    ..Collectively, our results indicated that DNA-PK promotes the establishment of a repressive chromatin at a TR target promoter by enhancing the HDAC activity of the receptor-bound NCoR/SMRT corepressor complex. ..
  50. Windhofer F, Wu W, Iliakis G. Low levels of DNA ligases III and IV sufficient for effective NHEJ. J Cell Physiol. 2007;213:475-83 pubmed
    ..We report that 70-80% knock down of LIG3 expression has no detectable effect on DSB rejoining, either in D-NHEJ proficient cells, or in cells where D-NHEJ ..
  51. Parsons J, Tait P, Finch D, Dianova I, Allinson S, Dianov G. CHIP-mediated degradation and DNA damage-dependent stabilization regulate base excision repair proteins. Mol Cell. 2008;29:477-87 pubmed publisher
    ..These data identify a molecular mechanism controlling cellular levels of BER enzymes and correspondingly the efficiency and capacity of BER. ..
  52. Doksani Y, de Lange T. Telomere-Internal Double-Strand Breaks Are Repaired by Homologous Recombination and PARP1/Lig3-Dependent End-Joining. Cell Rep. 2016;17:1646-1656 pubmed publisher
    ..However, as resected telomere-internal DSBs have perfect homology, their PARP1/Lig3-dependent end-joining may be more akin to single strand break repair...
  53. Grawunder U, Zimmer D, Fugmann S, Schwarz K, Lieber M. DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes. Mol Cell. 1998;2:477-84 pubmed
    ..Hence, DNA ligase IV is the activity responsible for the ligation step in NHEJ and in V(D)J recombination. ..
  54. Ho E, Satoh M. Repair of single-strand DNA interruptions by redundant pathways and its implication in cellular sensitivity to DNA-damaging agents. Nucleic Acids Res. 2003;31:7032-40 pubmed
    ..Thus, repair pathways mediated by Lig III may have a role in the regulation of cellular sensitivity to DNA-damaging agents. ..
  55. McNally J, O Brien P. Kinetic analyses of single-stranded break repair by human DNA ligase III isoforms reveal biochemical differences from DNA ligase I. J Biol Chem. 2017;292:15870-15879 pubmed publisher
    ..The LIG3 gene encodes a ubiquitous isoform in all tissues (LIG3?) and a germ line-specific splicing isoform (LIG3?) that ..
  56. Taylor R, Wickstead B, Cronin S, Caldecott K. Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1. Curr Biol. 1998;8:877-80 pubmed
    ..In summary, these data demonstrate that a BRCT domain can mediate a biologically important protein-protein interaction, and support the existence of additional roles. ..
  57. Liang L, Deng L, Nguyen S, Zhao X, Maulion C, Shao C, et al. Human DNA ligases I and III, but not ligase IV, are required for microhomology-mediated end joining of DNA double-strand breaks. Nucleic Acids Res. 2008;36:3297-310 pubmed publisher
    ..These data indicate that DNA ligases I and III are required in MHEJ. DNA ligase IV, on the contrary, is not required in MHEJ but facilitates Ku-dependent NHEJ. Therefore, MHEJ and NHEJ require different DNA ligases. ..
  58. Dulic A, Bates P, Zhang X, Martin S, Freemont P, Lindahl T, et al. BRCT domain interactions in the heterodimeric DNA repair protein XRCC1-DNA ligase III. Biochemistry. 2001;40:5906-13 pubmed
    ..These data identify the XRCC1-DNA ligase III heterodimer interface and provide the first demonstration of the surface contacts coordinating a functional BRCT-BRCT protein interaction. ..
  59. Sallmyr A, Tomkinson A, Rassool F. Up-regulation of WRN and DNA ligase IIIalpha in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks. Blood. 2008;112:1413-23 pubmed publisher
    ..We suggest that, although the repair of ROS-induced DSBs by this pathway contributes to the survival of CML cells, the resultant genomic instability drives disease progression. ..
  60. Ogi T, Limsirichaikul S, Overmeer R, Volker M, Takenaka K, Cloney R, et al. Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Mol Cell. 2010;37:714-27 pubmed publisher
    ..The remaining repair synthesis is dependent on pol epsilon, recruitment of which is dependent on the alternative clamp loader CTF18-RFC. ..
  61. Akbari M, Keijzers G, Maynard S, Scheibye Knudsen M, Desler C, Hickson I, et al. Overexpression of DNA ligase III in mitochondria protects cells against oxidative stress and improves mitochondrial DNA base excision repair. DNA Repair (Amst). 2014;16:44-53 pubmed publisher
  62. Ruhanen H, Ushakov K, Yasukawa T. Involvement of DNA ligase III and ribonuclease H1 in mitochondrial DNA replication in cultured human cells. Biochim Biophys Acta. 2011;1813:2000-7 pubmed publisher
    ..This study thus proposes that the mitochondrial replication system utilises distinct proteins, DNA ligase III and RNase H1, for Okazaki fragment maturation. ..
  63. Fernández Díez C, González Rojo S, Lombó M, Herraez M. Impact of sperm DNA damage and oocyte-repairing capacity on trout development. Reproduction. 2016;152:57-67 pubmed publisher
    ..Gene expression showed in out-of-season oocytes the overexpression of repair genes (ogg1, ung, lig3, rad1) and downregulation of tp53, indicating an enhanced repairing activity and reduced capacity to arrest ..
  64. Murray R, Tanteles G, Mills J, Perry A, Peat I, Osman A, et al. Association between single nucleotide polymorphisms in the DNA repair gene LIG3 and acute adverse skin reactions following radiotherapy. Radiother Oncol. 2011;99:231-4 pubmed publisher
    ..Using our cohort of 480 breast cancer patients, we provide replicated evidence that a polymorphism near the LIG3 gene is associated with acute skin toxicity following radiotherapy.
  65. Wiederhold L, Leppard J, Kedar P, Karimi Busheri F, Rasouli Nia A, Weinfeld M, et al. AP endonuclease-independent DNA base excision repair in human cells. Mol Cell. 2004;15:209-20 pubmed
    ..That NEIL1/PNK could also repair the products of other DNA glycosylases suggests a broad role for this APE-independent BER pathway in mammals. ..
  66. Yu Y, Tan R, Ren Q, Gao B, Sheng Z, Zhang J, et al. POT1 inhibits the efficiency but promotes the fidelity of nonhomologous end joining at non-telomeric DNA regions. Aging (Albany NY). 2017;9:2529-2543 pubmed publisher
    ..In addition, we found that overexpression of POT1 inhibits the protein stability of Lig3, which is the major regulator of alternative NHEJ (alt-NHEJ), therefore suppressing the efficiency of alt-NHEJ...
  67. Jones R, Oh S, Grimstead J, Zimbric J, Roger L, Heppel N, et al. Escape from telomere-driven crisis is DNA ligase III dependent. Cell Rep. 2014;8:1063-76 pubmed publisher
    ..We demonstrate that there is an absolute requirement for fully functional DNA ligase III (LIG3), but not ligase IV (LIG4), to facilitate the escape from a telomere-driven crisis...
  68. Li Z, Zhang W, Chen Y, Guo W, Zhang J, Tang H, et al. Impaired DNA double-strand break repair contributes to the age-associated rise of genomic instability in humans. Cell Death Differ. 2016;23:1765-1777 pubmed publisher
    ..Mechanistic analysis suggests that decreased expression of XRCC4, Lig4 and Lig3 drives the observed, age-associated decline of NHEJ efficiency and fidelity...
  69. Singh P, Mistry K. A computational approach to determine susceptibility to cancer by evaluating the deleterious effect of nsSNP in XRCC1 gene on binding interaction of XRCC1 protein with ligase III. Gene. 2016;576:141-9 pubmed publisher
    ..the most damaging nsSNPs using a computational approach and analysed its functional impact on the XRCC1 and LIG3 interaction...
  70. Muvarak N, Kelley S, Robert C, Baer M, Perrotti D, Gambacorti Passerini C, et al. c-MYC Generates Repair Errors via Increased Transcription of Alternative-NHEJ Factors, LIG3 and PARP1, in Tyrosine Kinase-Activated Leukemias. Mol Cancer Res. 2015;13:699-712 pubmed publisher alternative form of NHEJ (ALT-NHEJ) predominates, evidenced by increased expression of DNA ligase IIIα (LIG3) and PARP1, increased frequency of large genomic deletions, and repair using DNA sequence microhomologies...
  71. Tomkinson A, Mackey Z. Structure and function of mammalian DNA ligases. Mutat Res. 1998;407:1-9 pubmed
    ..DNA ligase activities, I-V, have been purified from mammalian cell extracts and three mammalian LIG genes, LIG1 LIG3 and LIG4, have been cloned...
  72. Dowling J, Becker C, Bourke N, Corr S, Connolly D, Quinn S, et al. Promyelocytic leukemia protein interacts with the apoptosis-associated speck-like protein to limit inflammasome activation. J Biol Chem. 2014;289:6429-37 pubmed publisher
    ..Collectively, our data indicate that PML limits ASC function, retaining ASC in the nucleus. ..
  73. Cotner Gohara E, Kim I, Hammel M, Tainer J, Tomkinson A, Ellenberger T. Human DNA ligase III recognizes DNA ends by dynamic switching between two DNA-bound states. Biochemistry. 2010;49:6165-76 pubmed publisher
    ..This work has implications for the biological specificity of DNA ligases and functions of PARP-like zinc fingers. ..
  74. Li D, Suzuki H, Liu B, Morris J, Liu J, Okazaki T, et al. DNA repair gene polymorphisms and risk of pancreatic cancer. Clin Cancer Res. 2009;15:740-6 pubmed publisher
    ..We analyzed 9 single nucleotide polymorphisms of 7 DNA repair genes (LIG3, LIG4, OGG1, ATM, POLB, RAD54L, and RECQL) in 734 patients with pancreatic adenocarcinoma and 780 healthy controls ..
  75. Figueroa J, Malats N, Real F, Silverman D, Kogevinas M, Chanock S, et al. Genetic variation in the base excision repair pathway and bladder cancer risk. Hum Genet. 2007;121:233-42 pubmed
    ..polymorphisms (SNPs) in 12 BER genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1, and LIG3)...
  76. Moreno V, Gemignani F, Landi S, Gioia Patricola L, Chabrier A, Blanco I, et al. Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Clin Cancer Res. 2006;12:2101-8 pubmed
    ..The candidate genes belong to different DNA repair pathways: base excision repair (OGG1, LIG3, APEX, POLB, XRCC1, PCNA, and MUTYH), nucleotide excision repair (ERCC1, ERCC2, ERCC4, and ERCC5), double-strand ..
  77. Zienolddiny S, Campa D, Lind H, Ryberg D, Skaug V, Stangeland L, et al. Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis. 2006;27:560-7 pubmed
    ..ERCC4/XPF and ERCC5/XPG; base excision repair (BER) genes APE1/APEX, OGG1, MPG, XRCC1, PCNA, POLB, POLiota, LIG3 and EXO1; double-strand break repair (DSB-R) genes XRCC2, XRCC3, XRCC9, NBS1 and ATR; and direct damage reversal (..
  78. Okano S, Lan L, Tomkinson A, Yasui A. Translocation of XRCC1 and DNA ligase IIIalpha from centrosomes to chromosomes in response to DNA damage in mitotic human cells. Nucleic Acids Res. 2005;33:422-9 pubmed
  79. Luo H, Chan D, Yang T, Rodriguez M, Chen B, Leng M, et al. A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment. Mol Cell Biol. 2004;24:8356-65 pubmed
    ..One complex contains known enzymes that are important for SSBR, including DNA ligase 3 (DNL3), polynucleotide kinase 3'-phosphatase, and polymerase beta; the other is a new complex that contains ..
  80. Hao B, Wang H, Zhou K, Li Y, Chen X, Zhou G, et al. Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma. Cancer Res. 2004;64:4378-84 pubmed
    ..4 SNPs, including 2 in the coding regions (ADPRT Val762Ala and MBD4 Glu346Lys) and others in noncoding regions (LIG3 A3704G and XRCC1 T-77C), remained as significant predictors for the risk of ESCC. The adjusted odd ratios were 1...