dna ligases


Summary: Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC (ATP) and EC (NAD).

Top Publications

  1. Yue J, Lu H, Lan S, Liu J, Stein M, Haffty B, et al. Identification of the DNA repair defects in a case of Dubowitz syndrome. PLoS ONE. 2013;8:e54389 pubmed publisher
    ..These data suggests that at least subset of Dubowitz syndrome can be attributed to DNA ligase IV mutations...
  2. Srivastava M, Nambiar M, Sharma S, Karki S, Goldsmith G, Hegde M, et al. An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell. 2012;151:1474-87 pubmed publisher
    ..This inhibitor to target NHEJ offers a strategy toward the treatment of cancer and improvement of existing regimens. ..
  3. Bombarde O, Boby C, Gomez D, Frit P, Giraud Panis M, Gilson E, et al. TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends. EMBO J. 2010;29:1573-84 pubmed publisher
    ..Thus, telomeres are protected against EJ by a lock with two bolts. These results account for observations with mammalian models and underline the importance of alternative non-classical EJ pathways for telomere fusions in cells. ..
  4. Li Z, Wen J, Lin Y, Wang S, Xue P, Zhang Z, et al. A Sir2-like protein participates in mycobacterial NHEJ. PLoS ONE. 2011;6:e20045 pubmed publisher
    ..Our results suggest that Sir2 may function closely together with Ku and LigD in the nonhomologous end-joining pathway in mycobacteria...
  5. Piserchio A, Nair P, Shuman S, Ghose R. Solution NMR studies of Chlorella virus DNA ligase-adenylate. J Mol Biol. 2010;395:291-308 pubmed publisher
    b>DNA ligases are essential guardians of genome integrity by virtue of their ability to recognize and seal 3'-OH/5'-phosphate nicks in duplex DNA...
  6. Nair P, Smith P, Shuman S. Structure of bacterial LigD 3'-phosphoesterase unveils a DNA repair superfamily. Proc Natl Acad Sci U S A. 2010;107:12822-7 pubmed publisher
    ..The PE active site and mechanism are unique vis à vis other end-healing enzymes. We find PE homologs in archaeal and eukaryal proteomes, signifying that PEs comprise a DNA repair superfamily. ..
  7. Tadeo X, López Méndez B, Trigueros T, Laín A, Castaño D, Millet O. Structural basis for the aminoacid composition of proteins from halophilic archea. PLoS Biol. 2009;7:e1000257 pubmed publisher
    ..Conversely, we quantitatively demonstrate that halophilicity is directly related to a decrease in the accessible surface area. ..
  8. Crut A, Nair P, Koster D, Shuman S, Dekker N. Dynamics of phosphodiester synthesis by DNA ligase. Proc Natl Acad Sci U S A. 2008;105:6894-9 pubmed publisher
    ..The estimated rate of phosphodiester synthesis by DNA ligase (400 s(-1)) is similar to the high rates of phosphodiester synthesis by replicative DNA polymerases. ..
  9. Ferrer M, Golyshina O, Beloqui A, Böttger L, Andreu J, Polaina J, et al. A purple acidophilic di-ferric DNA ligase from Ferroplasma. Proc Natl Acad Sci U S A. 2008;105:8878-83 pubmed publisher
    ..b>DNA ligases from closest phylogenetic and ecophysiological relatives have normal pH optima (6.0-7...

More Information


  1. Nijnik A, Dawson S, Crockford T, Woodbine L, Visetnoi S, Bennett S, et al. Impaired lymphocyte development and antibody class switching and increased malignancy in a murine model of DNA ligase IV syndrome. J Clin Invest. 2009;119:1696-705 pubmed publisher
    ..These findings provide explanations for the complex lymphoid phenotype of human LigIV syndrome. ..
  2. 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
    Mammalian cells have three ATP-dependent DNA ligases, which are required for DNA replication and repair...
  3. Williams E, Klingler R, Ponnaiya B, Hardt T, Schrock E, Lees Miller S, et al. Telomere dysfunction and DNA-PKcs deficiency: characterization and consequence. Cancer Res. 2009;69:2100-7 pubmed publisher
    ..These studies provide the first direct evidence of genetic susceptibility and environmental insult interactions leading to a unique and ongoing form of genomic instability capable of driving carcinogenesis. ..
  4. Odell I, Barbour J, MURPHY D, Della Maria J, Sweasy J, Tomkinson A, et al. Nucleosome disruption by DNA ligase III-XRCC1 promotes efficient base excision repair. Mol Cell Biol. 2011;31:4623-32 pubmed publisher
    ..Collectively, these findings provide insights into rate-limiting steps that govern BER in chromatin and reveal a unique role for ligase III?-XRCC1 in enhancing the efficiency of the final two steps in the BER of lesions in nucleosomes. ..
  5. Tavana O, Puebla Osorio N, Sang M, Zhu C. Absence of p53-dependent apoptosis combined with nonhomologous end-joining deficiency leads to a severe diabetic phenotype in mice. Diabetes. 2010;59:135-42 pubmed publisher
    ..This is a model that connects impaired DNA repair and accumulative DNA damage, a common phenotype in aging individuals, to the onset of diabetes. ..
  6. Lohman G, Chen L, Evans T. Kinetic characterization of single strand break ligation in duplex DNA by T4 DNA ligase. J Biol Chem. 2011;286:44187-96 pubmed publisher
    ..Pre-steady state reactions displayed a clear burst phase, consistent with this conclusion...
  7. Simsek D, Jasin M. DNA ligase III: a spotty presence in eukaryotes, but an essential function where tested. Cell Cycle. 2011;10:3636-44 pubmed publisher
    b>DNA ligases are crucial for most DNA transactions, including DNA replication, repair, and recombination. Recently, DNA ligase III (Lig3) has been demonstrated to be crucial for cell survival due to its catalytic function in mitochondria...
  8. Pardo B, Gómez González B, Aguilera A. DNA repair in mammalian cells: DNA double-strand break repair: how to fix a broken relationship. Cell Mol Life Sci. 2009;66:1039-56 pubmed publisher
    ..Here we briefly describe how eukaryotic cells sense DSBs and trigger cell cycle arrest to allow repair, and we review the mechanisms of both NHEJ and HR pathways and the choice between them. (Part of a Multi-author Review). ..
  9. Roy S, Andres S, Vergnes A, Neal J, Xu Y, Yu Y, et al. XRCC4's interaction with XLF is required for coding (but not signal) end joining. Nucleic Acids Res. 2012;40:1684-94 pubmed publisher
    ..Finally, DNA-PK phosphorylation of XRCC4/XLF complexes disrupt DNA bridging in vitro, suggesting a regulatory role for DNA-PK's phosphorylation of XRCC4/XLF complexes. ..
  10. Clerici M, Mantiero D, Guerini I, Lucchini G, Longhese M. The Yku70-Yku80 complex contributes to regulate double-strand break processing and checkpoint activation during the cell cycle. EMBO Rep. 2008;9:810-8 pubmed publisher
    ..Moreover, DSB resection in ykuDelta cells occurs independently of CDK activity, suggesting that it might be promoted by CDK-dependent inhibition of Yku. ..
  11. Simsek D, Jasin M. Alternative end-joining is suppressed by the canonical NHEJ component Xrcc4-ligase IV during chromosomal translocation formation. Nat Struct Mol Biol. 2010;17:410-6 pubmed publisher
    ..Complex insertions in some junctions show that joining can be iterative, encompassing successive processing steps before joining. Our results imply that alt-NHEJ is the primary mediator of translocation formation in mammalian cells. ..
  12. Andres S, Vergnes A, Ristic D, Wyman C, Modesti M, Junop M. A human XRCC4-XLF complex bridges DNA. Nucleic Acids Res. 2012;40:1868-78 pubmed publisher
    ..Based on these data and the crystal structure of an extended protein filament of XRCC4-XLF at 3.94?Å, a model for XRCC4-XLF complex function in NHEJ is presented. ..
  13. Malu S, De Ioannes P, Kozlov M, Greene M, Francis D, Hanna M, et al. Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs. J Exp Med. 2012;209:955-63 pubmed publisher
    ..Signal joint formation remains unaffected. Our data reveal that the C-terminal region of Artemis influences V(D)J recombination through its interaction with both Ligase IV and DNA-PKcs. ..
  14. Tanabe M, Ishino S, Yohda M, Morikawa K, Ishino Y, Nishida H. Structure-based mutational study of an archaeal DNA ligase towards improvement of ligation activity. Chembiochem. 2012;13:2575-82 pubmed publisher
    b>DNA ligases catalyze the joining of strand breaks in duplex DNA...
  15. Berg E, Christensen M, Dalla Rosa I, Wannagat E, Janicke R, Rösner L, et al. XRCC4 controls nuclear import and distribution of Ligase IV and exchanges faster at damaged DNA in complex with Ligase IV. DNA Repair (Amst). 2011;10:1232-42 pubmed publisher
  16. Paran N, De Silva F, Senkevich T, Moss B. Cellular DNA ligase I is recruited to cytoplasmic vaccinia virus factories and masks the role of the vaccinia ligase in viral DNA replication. Cell Host Microbe. 2009;6:563-9 pubmed publisher
    ..Encoding its own ligase might allow VACV to "jump-start" DNA synthesis. ..
  17. Bahmed K, Nitiss K, Nitiss J. Yeast Tdp1 regulates the fidelity of nonhomologous end joining. Proc Natl Acad Sci U S A. 2010;107:4057-62 pubmed publisher
  18. Hammel M, Yu Y, Fang S, Lees Miller S, Tainer J. XLF regulates filament architecture of the XRCC4·ligase IV complex. Structure. 2010;18:1431-42 pubmed publisher
    ..Collective results identify XRCC4 and XLF filaments suitable to align DNA molecules and function to facilitate LigIV end joining required for DSB repair in vivo. ..
  19. Cuneo M, Gabel S, Krahn J, Ricker M, London R. The structural basis for partitioning of the XRCC1/DNA ligase III-? BRCT-mediated dimer complexes. Nucleic Acids Res. 2011;39:7816-27 pubmed publisher
    ..These data provide fundamental insights into the structural basis of BRCT-mediated dimerization, and resolve questions related to the organization of this important repair complex. ..
  20. Palmbos P, Wu D, Daley J, Wilson T. Recruitment of Saccharomyces cerevisiae Dnl4-Lif1 complex to a double-strand break requires interactions with Yku80 and the Xrs2 FHA domain. Genetics. 2008;180:1809-19 pubmed publisher
    ..The collected results indicate that the Xrs-Lif1 and Yku80-Dnl4 interactions are important for formation of a productive ligase-DSB intermediate. ..
  21. Gao Y, Katyal S, Lee Y, Zhao J, Rehg J, Russell H, et al. DNA ligase III is critical for mtDNA integrity but not Xrcc1-mediated nuclear DNA repair. Nature. 2011;471:240-4 pubmed publisher
    DNA replication and repair in mammalian cells involves three distinct DNA ligases: ligase I (Lig1), ligase III (Lig3) and ligase IV (Lig4)...
  22. Chen X, Tomkinson A. Yeast Nej1 is a key participant in the initial end binding and final ligation steps of nonhomologous end joining. J Biol Chem. 2011;286:4931-40 pubmed publisher
  23. 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. ..
  24. Jayaram S, Ketner G, Adachi N, Hanakahi L. Loss of DNA ligase IV prevents recognition of DNA by double-strand break repair proteins XRCC4 and XLF. Nucleic Acids Res. 2008;36:5773-86 pubmed publisher
    ..These data suggest that the intrinsic DNA-binding activities of XRCC4 and XLF may be subject to regulation and are down regulated in human cells that lack ligase IV. ..
  25. Riballo E, Woodbine L, Stiff T, Walker S, Goodarzi A, Jeggo P. XLF-Cernunnos promotes DNA ligase IV-XRCC4 re-adenylation following ligation. Nucleic Acids Res. 2009;37:482-92 pubmed publisher
    ..We propose a model in which XLF, by in situ recharging DNA ligase IV after the first ligation event, promotes double stranded ligation by a single LX complex. ..
  26. Nelissen F, van Gammeren A, Tessari M, Girard F, Heus H, Wijmenga S. Multiple segmental and selective isotope labeling of large RNA for NMR structural studies. Nucleic Acids Res. 2008;36:e89 pubmed publisher
    ..The demonstrated multiple segmental labeling protocols are generally applicable to large RNA molecules and can be extended to more than three segments. ..
  27. Rossi M, Carbone M, Mostocotto C, Mancone C, Tripodi M, Maione R, et al. Mitochondrial localization of PARP-1 requires interaction with mitofilin and is involved in the maintenance of mitochondrial DNA integrity. J Biol Chem. 2009;284:31616-24 pubmed publisher
    ..This work highlights a new environment for PARP-1, opening the possibility that at least some of the nuclear functions of the enzyme can be also extended to mtDNA metabolism. ..
  28. Hsiao S, Smith S. Sister telomeres rendered dysfunctional by persistent cohesion are fused by NHEJ. J Cell Biol. 2009;184:515-26 pubmed publisher
    ..These results demonstrate that the timely removal of sister telomere cohesion is essential for the formation of a protective structure at chromosome ends after DNA replication in S/G2 phase of the cell cycle. ..
  29. 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
    ..While numerous studies have identified protein partners of the human DNA ligases (hLigs), there has been little characterization of the catalytic properties of these enzymes...
  30. de Boer P, Bastiaans J, Touw H, Kerkman R, Bronkhof J, van den Berg M, et al. Highly efficient gene targeting in Penicillium chrysogenum using the bi-partite approach in deltalig4 or deltaku70 mutants. Fungal Genet Biol. 2010;47:839-46 pubmed publisher
    ..chrysogenum genome. We expect that this combined approach will function with similar high efficiencies in other filamentous fungi. ..
  31. 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. ..
  32. Cottarel J, Frit P, Bombarde O, Salles B, Négrel A, Bernard S, et al. A noncatalytic function of the ligation complex during nonhomologous end joining. J Cell Biol. 2013;200:173-86 pubmed publisher
    ..We propose that productive end joining occurs by early formation of a supramolecular entity containing both DNA-PK and X4LIG4-Cer-XLF complexes on DNA ends. ..
  33. Vijayakumar S, Dziegielewska B, Levin D, Song W, Yin J, Yang A, et al. Phosphorylation of human DNA ligase I regulates its interaction with replication factor C and its participation in DNA replication and DNA repair. Mol Cell Biol. 2009;29:2042-52 pubmed publisher
    ..Thus, appropriate phosphorylation of hLigI is critical for its participation in DNA replication and repair. ..
  34. 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
    ..In this study, we used a cell-free assay to determine the roles of DNA ligases I, III and IV in MHEJ and NHEJ...
  35. Boboila C, Jankovic M, Yan C, Wang J, Wesemann D, Zhang T, et al. Alternative end-joining catalyzes robust IgH locus deletions and translocations in the combined absence of ligase 4 and Ku70. Proc Natl Acad Sci U S A. 2010;107:3034-9 pubmed publisher
    ..IgH chromosomal translocations to the c-myc oncogene also are augmented in the combined absence of Ku70 and ligase 4. We discuss the implications of these findings for A-EJ in normal and abnormal DSB repair. ..
  36. Dutta K, Natarajan A, Nair P, Shuman S, Ghose R. Sequence-specific 1H, 13C and 15N assignments of the phosphoesterase (PE) domain of Pseudomonas aeruginosa DNA ligase D (LigD). Biomol NMR Assign. 2011;5:151-5 pubmed publisher
    ..LigD PE exemplifies a structurally and mechanistically unique class of DNA end-processing enzymes. Here, we present the resonance assignments of the PE domain of Pseudomonas aeruginosa LigD comprising the N-terminal 177 residues. ..
  37. Conze T, Shetye A, Tanaka Y, Gu J, Larsson C, Göransson J, et al. Analysis of genes, transcripts, and proteins via DNA ligation. Annu Rev Anal Chem (Palo Alto Calif). 2009;2:215-39 pubmed publisher
    Analytical reactions in which short DNA strands are used in combination with DNA ligases have proven useful for measuring, decoding, and locating most classes of macromolecules...
  38. Han L, Yu K. Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV-deficient B cells. J Exp Med. 2008;205:2745-53 pubmed publisher
    ..The data revealed a fast-acting NHEJ and a slow-acting alterative end joining of switch region breaks during CSR. ..
  39. Chiruvella K, Sebastian R, Sharma S, Karande A, Choudhary B, Raghavan S. Time-dependent predominance of nonhomologous DNA end-joining pathways during embryonic development in mice. J Mol Biol. 2012;417:197-211 pubmed publisher
    ..Thus, our results establish for the first time the existence of both canonical and alternative NHEJ pathways during the postimplantation stages of mammalian embryonic development. ..
  40. Deng Y, Guo X, Ferguson D, Chang S. Multiple roles for MRE11 at uncapped telomeres. Nature. 2009;460:914-8 pubmed publisher
    ..MRE11 can also protect newly replicated leading strand telomeres from NHEJ by promoting 5' strand resection to generate POT1a-TPP1-bound 3' overhangs...
  41. Stein V, Hollfelder F. An efficient method to assemble linear DNA templates for in vitro screening and selection systems. Nucleic Acids Res. 2009;37:e122 pubmed publisher
    ..This fast and robust method should find widespread application in directed evolution for the assembly of gene libraries and the regeneration of linear DNA templates between successive screening and selection cycles. ..
  42. Chistiakov D, Voronova N, Chistiakov A. Ligase IV syndrome. Eur J Med Genet. 2009;52:373-8 pubmed publisher
    ..A truncating mutation R580X and a frameshift mutation K424FS resulting in loss of the C-terminal XRCC4-binding domain have deleterious effect on both expression and function of LIG4 and represent a null allele. ..
  43. Arefian E, Kiani J, Soleimani M, Shariati S, Aghaee Bakhtiari S, Atashi A, et al. Analysis of microRNA signatures using size-coded ligation-mediated PCR. Nucleic Acids Res. 2011;39:e80 pubmed publisher
    ..We conclude that the method can efficiently reveal miRNA signatures in a range of biological samples. ..
  44. Yutin N, Koonin E. Evolution of DNA ligases of nucleo-cytoplasmic large DNA viruses of eukaryotes: a case of hidden complexity. Biol Direct. 2009;4:51 pubmed publisher
    ..However, the details of the evolution of these genes that bear on the complexity of the putative ancestral NCLDV and on the evolutionary relationships between viruses and their hosts are not well understood...
  45. Liang X, Fujioka K, Asanuma H. Nick sealing by T4 DNA ligase on a modified DNA template: tethering a functional molecule on D-threoninol. Chemistry. 2011;17:10388-96 pubmed publisher
    ..The biological significance of this unexpected enzymatic action is also discussed on the basis of kinetic analysis. ..
  46. Reynolds J, El Khamisy S, Katyal S, Clements P, McKinnon P, Caldecott K. Defective DNA ligation during short-patch single-strand break repair in ataxia oculomotor apraxia 1. Mol Cell Biol. 2009;29:1354-62 pubmed publisher
    ..These data demonstrate that aprataxin participates in chromosomal SSBR in vivo and suggest that short-patch SSBR arrests in AOA1 because of insufficient nonadenylated DNA ligase. ..
  47. Wu P, Frit P, Meesala S, Dauvillier S, Modesti M, Andres S, et al. Structural and functional interaction between the human DNA repair proteins DNA ligase IV and XRCC4. Mol Cell Biol. 2009;29:3163-72 pubmed publisher
    ..Together our findings provide unanticipated insight for understanding the physical and functional architecture of the nonhomologous end-joining ligation complex. ..
  48. Ochi T, Wu Q, Chirgadze D, Grossmann J, Bolanos Garcia V, Blundell T. Structural insights into the role of domain flexibility in human DNA ligase IV. Structure. 2012;20:1212-22 pubmed publisher
    ..Our results suggest that the flexibility of the catalytic region is limited in a manner that affects the formation of the LigIV/XRCC4/XLF-Cernunnos complex. ..
  49. van der Burg M, Ijspeert H, Verkaik N, Turul T, Wiegant W, Morotomi Yano K, et al. A DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining. J Clin Invest. 2009;119:91-8 pubmed publisher
    ..Further, the data suggest that residual DNA-PKcs activity is indispensable in humans. ..
  50. Samai P, Shuman S. Structure-function analysis of the OB and latch domains of chlorella virus DNA ligase. J Biol Chem. 2011;286:22642-52 pubmed publisher
    ..Arg-285 is a key component of the OB-NTase interface, where it forms a salt bridge to the essential Asp-29 side chain, which is imputed to coordinate divalent metal catalysts during the nick sealing steps. ..
  51. 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.
  52. Arakawa H, Bednar T, Wang M, Paul K, Mladenov E, Bencsik Theilen A, et al. Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells. Nucleic Acids Res. 2012;40:2599-610 pubmed publisher
    In eukaryotes, the three families of ATP-dependent DNA ligases are associated with specific functions in DNA metabolism. DNA ligase I (LigI) catalyzes Okazaki-fragment ligation at the replication fork and nucleotide excision repair (NER)...
  53. Nakazawa T, Ando Y, Kitaaki K, Nakahori K, Kamada T. Efficient gene targeting in ?Cc.ku70 or ?Cc.lig4 mutants of the agaricomycete Coprinopsis cinerea. Fungal Genet Biol. 2011;48:939-46 pubmed publisher
    ..lig4 using the Cc.ku70 disruptant. We found that the disruption of Cc.ku70 or Cc.lig4 greatly enhanced gene targeting. In addition, this study demonstrates that Cc.wc-2 is involved in blue light perception in this fungus...