Gene Symbol: DNL4
Description: DNA ligase (ATP) DNL4
Alias: LIG4, DNA ligase (ATP) DNL4
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Doré A, Furnham N, Davies O, Sibanda B, Chirgadze D, Jackson S, et al. Structure of an Xrcc4-DNA ligase IV yeast ortholog complex reveals a novel BRCT interaction mode. DNA Repair (Amst). 2006;5:362-8 pubmed
    ..The structure reveals a novel mode of protein recognition by a tandem BRCT repeat, and in addition provides a molecular basis for a human LIG4 syndrome clinical condition.
  2. Wilson T, Grawunder U, Lieber M. Yeast DNA ligase IV mediates non-homologous DNA end joining. Nature. 1997;388:495-8 pubmed
    ..two typical DNA ligases, the known DNA ligase I homologue CDC9 and the previously unknown DNA ligase IV homologue DNL4. dnl4 mutants are deficient in precise and end-processed NHEJ...
  3. Herrmann G, Lindahl T, Schär P. Saccharomyces cerevisiae LIF1: a function involved in DNA double-strand break repair related to mammalian XRCC4. EMBO J. 1998;17:4188-98 pubmed
    Saccharomyces cerevisiae DNA ligase IV (LIG4) has been shown previously to be involved in non-homologous DNA end joining and meiosis...
  4. Matsuzaki K, Terasawa M, Iwasaki D, Higashide M, Shinohara M. Cyclin-dependent kinase-dependent phosphorylation of Lif1 and Sae2 controls imprecise nonhomologous end joining accompanied by double-strand break resection. Genes Cells. 2012;17:473-93 pubmed publisher
    ..CDK-dependent modification of the NHEJ pathway might make DSB ends compatible for NHEJ and thus prevent competition between HR and NHEJ in hierarchy on the choice of DSB repair pathways. ..
  5. Chen L, Trujillo K, Ramos W, Sung P, Tomkinson A. Promotion of Dnl4-catalyzed DNA end-joining by the Rad50/Mre11/Xrs2 and Hdf1/Hdf2 complexes. Mol Cell. 2001;8:1105-15 pubmed
    ..that the complex formed by Rad50, Mre11, and Xrs2 proteins promotes intermolecular DNA joining by DNA ligase IV (Dnl4) and its associated protein Lif1...
  6. Tseng H, Tomkinson A. A physical and functional interaction between yeast Pol4 and Dnl4-Lif1 links DNA synthesis and ligation in nonhomologous end joining. J Biol Chem. 2002;277:45630-7 pubmed
    ..Pol4 also interacts directly with the Dnl4 subunit of the Dnl4-Lif1 complex via its N-terminal BRCT domain...
  7. Matsuzaki K, Shinohara A, Shinohara M. Forkhead-associated domain of yeast Xrs2, a homolog of human Nbs1, promotes nonhomologous end joining through interaction with a ligase IV partner protein, Lif1. Genetics. 2008;179:213-25 pubmed publisher
    ..The FHA domain of Xrs2 specifically interacts with Lif1, a component of the ligase IV complex, Dnl4-Nej1-Lif1 (DNL). Lif1, which is phosphorylated in vivo, contains two Xrs2-binding regions...
  8. Schär P, Fäsi M, Jessberger R. SMC1 coordinates DNA double-strand break repair pathways. Nucleic Acids Res. 2004;32:3921-9 pubmed
    ..Strikingly, inactivation of RAD52 or RAD54 fully rescued efficiency and accuracy of NHEJ in the smc1 background. Therefore, we propose coordination of HR and NHEJ processes by Smc1p through interaction with the RAD52 pathway. ..
  9. Schär P, Herrmann G, Daly G, Lindahl T. A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks. Genes Dev. 1997;11:1912-24 pubmed
    ..shares significant amino acid sequence homology with human DNA ligase IV; accordingly, we designate the yeast gene LIG4. Recombinant LIG4 protein forms a covalent enzyme-AMP complex and can join a DNA single-strand break in a DNA/RNA ..

More Information


  1. 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
    ..Here, we show that a lack of any of the NHEJ proteins Yku (Yku70-Yku80), Lif1 or DNA ligase IV (Dnl4) increases 5' DSB end degradation in G1 phase, with ykuDelta cells showing the strongest effect...
  2. Zhang Y, Hefferin M, Chen L, Shim E, Tseng H, Kwon Y, et al. Role of Dnl4-Lif1 in nonhomologous end-joining repair complex assembly and suppression of homologous recombination. Nat Struct Mol Biol. 2007;14:639-46 pubmed
    ..there are pairwise physical interactions among the core complexes of the NHEJ pathway, namely Yku70-Yku80 (Ku), Dnl4-Lif1 and Mre11-Rad50-Xrs2 (MRX)...
  3. Deshpande R, Wilson T. Modes of interaction among yeast Nej1, Lif1 and Dnl4 proteins and comparison to human XLF, XRCC4 and Lig4. DNA Repair (Amst). 2007;6:1507-16 pubmed
    ..The implications of these findings for DNA ligase IV function are considered in light of the evolutionary pattern in the XLF/XRCC4 and XLF/Nej1 family. ..
  4. Teo S, Jackson S. Lif1p targets the DNA ligase Lig4p to sites of DNA double-strand breaks. Curr Biol. 2000;10:165-8 pubmed
    ..Furthermore, this targeting requires another key NHEJ protein, Ku. ..
  5. Palmbos P, Daley J, Wilson T. Mutations of the Yku80 C terminus and Xrs2 FHA domain specifically block yeast nonhomologous end joining. Mol Cell Biol. 2005;25:10782-90 pubmed
    ..three protein complexes in Saccharomyces cerevisiae: MRX (Mre11-Rad50-Xrs2), Ku (Ku70-Ku80), and DNA ligase IV (Dnl4-Lif1-Nej1)...
  6. Tseng H, Tomkinson A. Processing and joining of DNA ends coordinated by interactions among Dnl4/Lif1, Pol4, and FEN-1. J Biol Chem. 2004;279:47580-8 pubmed
    ..Pol4 and the DNA structure-specific endonuclease FEN-1(Rad27) in the processing of DNA ends to be joined by Dnl4/Lif1...
  7. Myung K, Chen C, Kolodner R. Multiple pathways cooperate in the suppression of genome instability in Saccharomyces cerevisiae. Nature. 2001;411:1073-6 pubmed
    ..Mutations that inactivate these pathways cause high rates of GCRs and show synergistic interactions, indicating that the pathways that suppress GCRs all compete for the same DNA substrates. ..
  8. Vigasová D, Sarangi P, Kolesar P, Vlasáková D, Slezakova Z, Altmannova V, et al. Lif1 SUMOylation and its role in non-homologous end-joining. Nucleic Acids Res. 2013;41:5341-53 pubmed publisher
    ..Taken together, these findings suggest that SUMOylation of Lif1 represents a new regulatory mechanism that downregulates NHEJ in a cell cycle phase-independent manner. ..
  9. Tam A, Pike B, Hammet A, Heierhorst J. Telomere-related functions of yeast KU in the repair of bleomycin-induced DNA damage. Biochem Biophys Res Commun. 2007;357:800-3 pubmed
  10. Sarangi P, Steinacher R, Altmannova V, Fu Q, Paull T, Krejci L, et al. Sumoylation influences DNA break repair partly by increasing the solubility of a conserved end resection protein. PLoS Genet. 2015;11:e1004899 pubmed publisher
    ..They also show that collaboration between different modifications and among multiple substrates leads to a stronger biological effect. ..
  11. Tseng S, Gabriel A, Teng S. Proofreading activity of DNA polymerase Pol2 mediates 3'-end processing during nonhomologous end joining in yeast. PLoS Genet. 2008;4:e1000060 pubmed publisher
    ..Indeed, a mutation in the 3'-5' exonuclease domain of Pol2 dramatically reduces the frequency of end joins formed with initial 3' flaps. Thus, Pol2 performs a key 3' end-processing step in NHEJ. ..
  12. Hwang J, Smith S, Ceschia A, Torres Rosell J, Aragon L, Myung K. Smc5-Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications. DNA Repair (Amst). 2008;7:1426-36 pubmed publisher
  13. Yang J, Freudenreich C. The Rtt109 histone acetyltransferase facilitates error-free replication to prevent CAG/CTG repeat contractions. DNA Repair (Amst). 2010;9:414-20 pubmed publisher
    ..On the other hand, Dnl4 and Rad51-dependent pathways did play a role in creating some of the repeat contractions in rtt109Delta cells...
  14. Faucher D, Wellinger R. Methylated H3K4, a transcription-associated histone modification, is involved in the DNA damage response pathway. PLoS Genet. 2010;6: pubmed publisher
    ..Given the high degree of conservation for the methyltransferase and the histone mark in a broad variety of organisms, these results could have similar implications for genome stability mechanisms in vertebrate and mammalian cells. ..
  15. Li X, Tye B. Ploidy dictates repair pathway choice under DNA replication stress. Genetics. 2011;187:1031-40 pubmed publisher
    ..In response to replication stress, early events associated with ploidy dictate the repair pathway choice. This study uncovers a fundamental difference between haplophase and diplophase in the maintenance of genome integrity. ..
  16. Putnam C, Pallis K, Hayes T, Kolodner R. DNA repair pathway selection caused by defects in TEL1, SAE2, and de novo telomere addition generates specific chromosomal rearrangement signatures. PLoS Genet. 2014;10:e1004277 pubmed publisher
    ..Interestingly, the inverted duplications observed here resemble common GCRs in metastatic pancreatic cancer. ..
  17. Gaillard H, Aguilera A. Cleavage factor I links transcription termination to DNA damage response and genome integrity maintenance in Saccharomyces cerevisiae. PLoS Genet. 2014;10:e1004203 pubmed publisher
    ..These findings reveal a new function for CFI in the DDR and underscore the importance of coordinating transcription termination with replication in the maintenance of genomic stability. ..
  18. Cheng X, Ivessa A. Accumulation of linear mitochondrial DNA fragments in the nucleus shortens the chronological life span of yeast. Eur J Cell Biol. 2012;91:782-8 pubmed publisher
    ..Here, we show that lack of the non-homologous-end-joining enzyme DNA ligase IV (DNL4) can rescue the short CLS of the yme1-1 mutant...
  19. Raykov V, Marvin M, Louis E, Maringele L. Telomere Dysfunction Triggers Palindrome Formation Independently of Double-Strand Break Repair Mechanisms. Genetics. 2016;203:1659-68 pubmed publisher
    ..We propose a model called short-inverted repeat-induced synthesis in which DNA synthesis, rather than DSB repair, drives the inverted duplication triggered by telomere dysfunction. ..
  20. Kelly M, Alver B, Kirkpatrick D. Minisatellite alterations in ZRT1 mutants occur via RAD52-dependent and RAD52-independent mechanisms in quiescent stationary phase yeast cells. DNA Repair (Amst). 2011;10:556-66 pubmed publisher
    ..We propose that the mechanism of ZRT1-mediated minisatellite instability during quiescence is relevant to human cells, and thus, human disease. ..
  21. Fritsch O, Burkhalter M, Kais S, Sogo J, Schär P. DNA ligase 4 stabilizes the ribosomal DNA array upon fork collapse at the replication fork barrier. DNA Repair (Amst). 2010;9:879-88 pubmed publisher
    ..fork stability is compromised, reveal a class of DSBs that are detectable only in the presence of functional Dnl4. Under these conditions, Dnl4 also limits the formation of extrachromosomal ribosomal DNA circles...
  22. Meyer D, Bailis A. Mating type influences chromosome loss and replicative senescence in telomerase-deficient budding yeast by Dnl4-dependent telomere fusion. Mol Microbiol. 2008;69:1246-54 pubmed publisher
  23. Vance J, Wilson T. Yeast Tdp1 and Rad1-Rad10 function as redundant pathways for repairing Top1 replicative damage. Proc Natl Acad Sci U S A. 2002;99:13669-74 pubmed
    ..Finally, we show that yeast lacking the Rad1-Rad10-related proteins Mus81-Mms4 display a unique pattern of camptothecin sensitivity and suggest a concerted model for the action of these endonucleases. ..
  24. Herrmann G, Kais S, Hoffbauer J, Shah Hosseini K, Brüggenolte N, Schober H, et al. Conserved interactions of the splicing factor Ntr1/Spp382 with proteins involved in DNA double-strand break repair and telomere metabolism. Nucleic Acids Res. 2007;35:2321-32 pubmed
    ..Like PinX1, NTR1 localizes to telomeres and associates with nucleoli in yeast and human cells, suggesting a function in localized control of DSBR. ..
  25. Miura T, Yamana Y, Usui T, Ogawa H, Yamamoto M, Kusano K. Homologous recombination via synthesis-dependent strand annealing in yeast requires the Irc20 and Srs2 DNA helicases. Genetics. 2012;191:65-78 pubmed publisher
    ..We propose that Irc20 and Mre11 functionally interact in the early steps of DSB repair and that Srs2 acts on the D-loops to lead to SDSA and to prevent crossoverv. ..
  26. Bonetti D, Anbalagan S, Lucchini G, Clerici M, Longhese M. Tbf1 and Vid22 promote resection and non-homologous end joining of DNA double-strand break ends. EMBO J. 2013;32:275-89 pubmed publisher
    ..Finally, inactivation of either Tbf1 or Vid22 impairs nucleosome eviction around the DSB, suggesting that these proteins promote efficient repair of the break by influencing chromatin identity in its surroundings. ..
  27. Chiruvella K, Liang Z, Birkeland S, Basrur V, Wilson T. Saccharomyces cerevisiae DNA ligase IV supports imprecise end joining independently of its catalytic activity. PLoS Genet. 2013;9:e1003599 pubmed publisher
    DNA ligase IV (Dnl4 in budding yeast) is a specialized ligase used in non-homologous end joining (NHEJ) of DNA double-strand breaks (DSBs)...
  28. Chiruvella K, Renard B, Birkeland S, Sunder S, Liang Z, Wilson T. Yeast DNA ligase IV mutations reveal a nonhomologous end joining function of BRCT1 distinct from XRCC4/Lif1 binding. DNA Repair (Amst). 2014;24:37-45 pubmed publisher
    LIG4/Dnl4 is the DNA ligase that (re)joins DNA double-strand breaks (DSBs) via nonhomologous end joining (NHEJ), an activity supported by binding of its tandem BRCT domains to the ligase accessory protein XRCC4/Lif1...
  29. Chen C, Motegi A, Hasegawa Y, Myung K, Kolodner R, D ANDREA A. Genetic analysis of ionizing radiation-induced mutagenesis in Saccharomyces cerevisiae reveals TransLesion Synthesis (TLS) independent of PCNA K164 SUMOylation and ubiquitination. DNA Repair (Amst). 2006;5:1475-88 pubmed
    ..A genetic model based on these observations is proposed. ..
  30. Valencia Burton M, Oki M, Johnson J, Seier T, Kamakaka R, Haber J. Different mating-type-regulated genes affect the DNA repair defects of Saccharomyces RAD51, RAD52 and RAD55 mutants. Genetics. 2006;174:41-55 pubmed
    ..All three recombination-defective mutations are made more sensitive by deletions of Rad6 and of the histone deacetylases Rpd3 and Ume6, although these mutations are not themselves CPT or phleomycin sensitive. ..