Gene Symbol: TOP3
Description: DNA topoisomerase 3
Alias: EDR1, DNA topoisomerase 3
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Chen C, Brill S. Binding and activation of DNA topoisomerase III by the Rmi1 subunit. J Biol Chem. 2007;282:28971-9 pubmed
    ..and oligosaccharide binding-fold protein that is associated with RecQ DNA helicase complexes from humans (BLM-TOP3 alpha) and yeast (Sgs1-Top3)...
  2. Mullen J, Nallaseth F, Lan Y, Slagle C, Brill S. Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex. Mol Cell Biol. 2005;25:4476-87 pubmed
    Genome stability requires a set of RecQ-Top3 DNA helicase-topoisomerase complexes whose sole budding yeast homolog is encoded by SGS1-TOP3...
  3. Watt P, Hickson I, Borts R, Louis E. SGS1, a homologue of the Bloom's and Werner's syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae. Genetics. 1996;144:935-45 pubmed
    ..meiosis I chromosome missegregation has been shown to be elevated sgs1 delta suppresses the slow growth of a top3 delta strain lacking topoisomerase III...
  4. Mullen J, Kaliraman V, Ibrahim S, Brill S. Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae. Genetics. 2001;157:103-18 pubmed
    ..None of these genes is required for viability and all SLX null mutations are synthetically lethal with mutations in TOP3, encoding the SGS1-interacting DNA topoisomerase...
  5. Chakraverty R, Kearsey J, Oakley T, Grenon M, de La Torre Ruiz M, Lowndes N, et al. Topoisomerase III acts upstream of Rad53p in the S-phase DNA damage checkpoint. Mol Cell Biol. 2001;21:7150-62 pubmed
    Deletion of the Saccharomyces cerevisiae TOP3 gene, encoding Top3p, leads to a slow-growth phenotype characterized by an accumulation of cells with a late S/G2 content of DNA (S. Gangloff, J. P. McDonald, C. Bendixen, L. Arthur, and R...
  6. Gangloff S, McDonald J, Bendixen C, Arthur L, Rothstein R. The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Mol Cell Biol. 1994;14:8391-8 pubmed
    We have previously shown that cells mutant for TOP3, a gene encoding a prokaryotic-like type I topoisomerase in Saccharomyces cerevisiae, display a pleiotropic phenotype including slow growth and genome instability...
  7. Chang M, Bellaoui M, Zhang C, Desai R, Morozov P, Delgado Cruzata L, et al. RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex. EMBO J. 2005;24:2024-33 pubmed
    ..gene RMI1 (RecQ-mediated genome instability, also known as NCE4 and YPL024W) was highly similar to that of SGS1 and TOP3, suggesting a functional relationship between Rmi1 and the Sgs1/Top3 complex...
  8. Bjergbaek L, Cobb J, Tsai Pflugfelder M, Gasser S. Mechanistically distinct roles for Sgs1p in checkpoint activation and replication fork maintenance. EMBO J. 2005;24:405-17 pubmed
  9. Mankouri H, Ngo H, Hickson I. Shu proteins promote the formation of homologous recombination intermediates that are processed by Sgs1-Rmi1-Top3. Mol Biol Cell. 2007;18:4062-73 pubmed
    ..identified in Saccharomyces cerevisiae as four genes in the same epistasis group that suppress various sgs1 and top3 mutant phenotypes when mutated...

More Information


  1. Menolfi D, Delamarre A, Lengronne A, Pasero P, Branzei D. Essential Roles of the Smc5/6 Complex in Replication through Natural Pausing Sites and Endogenous DNA Damage Tolerance. Mol Cell. 2015;60:835-46 pubmed publisher
  2. Bennett R, Noirot Gros M, Wang J. Interaction between yeast sgs1 helicase and DNA topoisomerase III. J Biol Chem. 2000;275:26898-905 pubmed
    ..In sgs1 top3 cells devoid of DNA topoisomerase III, however, expression of full-length Sgs1 or Sgs1 lacking the N-terminal 107 ..
  3. 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
    ..Consistently, dnl4 cells displayed altered fork structures at the replication fork barrier, leading us to propose an as yet unrecognized role for Dnl4 in the maintenance of ribosomal DNA stability. ..
  4. Torres J, Schnakenberg S, Zakian V. Saccharomyces cerevisiae Rrm3p DNA helicase promotes genome integrity by preventing replication fork stalling: viability of rrm3 cells requires the intra-S-phase checkpoint and fork restart activities. Mol Cell Biol. 2004;24:3198-212 pubmed
    ..Based on synthetic phenotypes, the intra-S-phase checkpoint, the SRS2 inhibitor of recombination, the SGS1/TOP3 replication fork restart pathway, and the MRE11/RAD50/XRS2 (MRX) complex were critical for viability of rrm3 cells...
  5. Niu H, Chung W, Zhu Z, Kwon Y, Zhao W, Chi P, et al. Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae. Nature. 2010;467:108-11 pubmed publisher
    ..DNA end-resection machinery comprising the Saccharomyces cerevisiae Mre11-Rad50-Xrs2 (MRX) complex, the Sgs1-Top3-Rmi1 complex, Dna2 protein and the heterotrimeric ssDNA-binding protein RPA...
  6. Bonner J, Choi K, Xue X, Torres N, Szakal B, Wei L, et al. Smc5/6 Mediated Sumoylation of the Sgs1-Top3-Rmi1 Complex Promotes Removal of Recombination Intermediates. Cell Rep. 2016;16:368-378 pubmed publisher
    ..The DNA helicase-topoisomerase complex, Sgs1-Top3-Rmi1 (STR), is the major pathway for processing these intermediates to generate conservative products...
  7. Moriel Carretero M, Aguilera A. A postincision-deficient TFIIH causes replication fork breakage and uncovers alternative Rad51- or Pol32-mediated restart mechanisms. Mol Cell. 2010;37:690-701 pubmed publisher
    ..Our results define the genetic and molecular hallmarks of replication fork breakage and restart and bring insights to understand specific NER-related human syndromes. ..
  8. Ii M, Ii T, Mironova L, Brill S. Epistasis analysis between homologous recombination genes in Saccharomyces cerevisiae identifies multiple repair pathways for Sgs1, Mus81-Mms4 and RNase H2. Mutat Res. 2011;714:33-43 pubmed publisher
    ..We conclude that SGS1 and MUS81 act in parallel pathways downstream of RAD51 and RAD52, respectively. The data further indicate these pathways share common components and display complex interactions. ..
  9. Fricke W, Kaliraman V, Brill S. Mapping the DNA topoisomerase III binding domain of the Sgs1 DNA helicase. J Biol Chem. 2001;276:8848-55 pubmed
    Several members of the RecQ family of DNA helicases are known to interact with DNA topoisomerase III (Top3)...
  10. Cejka P, Cannavo E, Polaczek P, Masuda Sasa T, Pokharel S, Campbell J, et al. DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2. Nature. 2010;467:112-6 pubmed publisher
    ..In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11-Rad50-Xrs2 complex (MRX) have important roles as stimulatory components...
  11. Sollier J, Driscoll R, Castellucci F, Foiani M, Jackson S, Branzei D. The Saccharomyces cerevisiae Esc2 and Smc5-6 proteins promote sister chromatid junction-mediated intra-S repair. Mol Biol Cell. 2009;20:1671-82 pubmed publisher
  12. Wang T, Kung W. Supercomplex formation between Mlh1-Mlh3 and Sgs1-Top3 heterocomplexes in meiotic yeast cells. Biochem Biophys Res Commun. 2002;296:949-53 pubmed
    ..Sgs1, a member of the RecQ DNA helicase family, appears to form a stable complex with topoisomerase III (Top3) during meiosis...
  13. Alzu A, Bermejo R, Begnis M, Lucca C, Piccini D, Carotenuto W, et al. Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes. Cell. 2012;151:835-846 pubmed publisher
  14. Bernstein K, Shor E, Sunjevaric I, Fumasoni M, Burgess R, Foiani M, et al. Sgs1 function in the repair of DNA replication intermediates is separable from its role in homologous recombinational repair. EMBO J. 2009;28:915-25 pubmed publisher
    ..The budding yeast Saccharomyces cerevisiae has one RecQ helicase, Sgs1, which functions with Top3 and Rmi1 in DNA repair...
  15. Kim R, Caron P, Wang J. Effects of yeast DNA topoisomerase III on telomere structure. Proc Natl Acad Sci U S A. 1995;92:2667-71 pubmed
    The yeast TOP3 gene, encoding DNA topoisomerase III, and EST1 gene, encoding a putative telomerase, are shown to be abutted head-to-head on chromosome XII, with the two initiation codons separated by 258 bp...
  16. Smith J, Chen Q, Yatsunyk L, Nicoludis J, Garcia M, Kranaster R, et al. Rudimentary G-quadruplex-based telomere capping in Saccharomyces cerevisiae. Nat Struct Mol Biol. 2011;18:478-85 pubmed publisher
    ..These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo. ..
  17. Shor E, Gangloff S, Wagner M, Weinstein J, Price G, Rothstein R. Mutations in homologous recombination genes rescue top3 slow growth in Saccharomyces cerevisiae. Genetics. 2002;162:647-62 pubmed
    In budding yeast, loss of topoisomerase III, encoded by the TOP3 gene, leads to a genomic instability phenotype that includes slow growth, hyper-sensitivity to genotoxic agents, mitotic hyper-recombination, increased chromosome ..
  18. Hishida T, Iwasaki H, Ohno T, Morishita T, Shinagawa H. A yeast gene, MGS1, encoding a DNA-dependent AAA(+) ATPase is required to maintain genome stability. Proc Natl Acad Sci U S A. 2001;98:8283-9 pubmed
    ..The mgs1 mutation is synergistic with a mutation in top3 (encoding topoisomerase III), and the double mutant exhibits severe growth defects and markedly increased genome ..
  19. Böhm S, Mihalevic M, Casal M, Bernstein K. Disruption of SUMO-targeted ubiquitin ligases Slx5-Slx8/RNF4 alters RecQ-like helicase Sgs1/BLM localization in yeast and human cells. DNA Repair (Amst). 2015;26:1-14 pubmed publisher
    ..Our results point to a model where RecQ-like helicase subcellular localization is regulated by STUbLs in response to DNA damage, presumably to prevent illegitimate recombination events. ..
  20. Chen C, Brill S. An essential DNA strand-exchange activity is conserved in the divergent N-termini of BLM orthologs. EMBO J. 2010;29:1713-25 pubmed publisher
    ..BLM is highly conserved and all BLM orthologs, including budding yeast Sgs1, have a large N-terminus that binds Top3-Rmi1 but has no known catalytic activity...
  21. Nielsen I, Bentsen I, Andersen A, Gasser S, Bjergbaek L. A Rad53 independent function of Rad9 becomes crucial for genome maintenance in the absence of the Recq helicase Sgs1. PLoS ONE. 2013;8:e81015 pubmed publisher
    ..checkpoint responses with relation to the requirement of the Sgs1 interacting partner Topoisomerase III (Top3)...
  22. Bailis A, Arthur L, Rothstein R. Genome rearrangement in top3 mutants of Saccharomyces cerevisiae requires a functional RAD1 excision repair gene. Mol Cell Biol. 1992;12:4988-93 pubmed
    Saccharomyces cerevisiae cells that are mutated at TOP3, a gene that encodes a protein homologous to bacterial type I topoisomerases, have a variety of defects, including reduced growth rate, altered gene expression, blocked sporulation, ..
  23. Torres Rosell J, Machin F, Farmer S, Jarmuz A, Eydmann T, Dalgaard J, et al. SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions. Nat Cell Biol. 2005;7:412-9 pubmed
    ..These results point towards a role for the Smc5-Smc6 complex in preventing the formation of sister chromatid junctions, thereby ensuring the correct partitioning of chromosomes during anaphase. ..
  24. Lai M, Seki M, Ui A, Enomoto T. Rmi1, a member of the Sgs1-Top3 complex in budding yeast, contributes to sister chromatid cohesion. EMBO Rep. 2007;8:685-90 pubmed
    ..protein was recently identified as the third member of the slow growth suppressor 1-DNA topoisomerase III (Sgs1-Top3) complex, which is required for maintaining genomic stability...
  25. Wagner M, Price G, Rothstein R. The absence of Top3 reveals an interaction between the Sgs1 and Pif1 DNA helicases in Saccharomyces cerevisiae. Genetics. 2006;174:555-73 pubmed
    ..In yeast, mutation of the TOP3 gene encoding Topo III causes pleiotropic defects that are suppressed by deletion of the RecQ homolog Sgs1...
  26. Kaur H, De Muyt A, Lichten M. Top3-Rmi1 DNA single-strand decatenase is integral to the formation and resolution of meiotic recombination intermediates. Mol Cell. 2015;57:583-594 pubmed publisher
    The topoisomerase III (Top3)-Rmi1 heterodimer, which catalyzes DNA single-strand passage, forms a conserved complex with the Bloom's helicase (BLM, Sgs1 in budding yeast)...
  27. Shor E, Weinstein J, Rothstein R. A genetic screen for top3 suppressors in Saccharomyces cerevisiae identifies SHU1, SHU2, PSY3 and CSM2: four genes involved in error-free DNA repair. Genetics. 2005;169:1275-89 pubmed
    ..In Saccharomyces cerevisiae, loss of the TOP3 gene, encoding topoisomerase III, results in a phenotype of slow growth, DNA damage sensitivity, meiotic defects, ..
  28. Ui A, Seki M, Ogiwara H, Onodera R, Fukushige S, Onoda F, et al. The ability of Sgs1 to interact with DNA topoisomerase III is essential for damage-induced recombination. DNA Repair (Amst). 2005;4:191-201 pubmed
    ..DNA helicase activity, and a mutant allele of SGS1 was identified as a suppressor of the slow growth phenotype of top3 mutants...
  29. Oakley T, Goodwin A, Chakraverty R, Hickson I. Inactivation of homologous recombination suppresses defects in topoisomerase III-deficient mutants. DNA Repair (Amst). 2002;1:463-82 pubmed
    The Saccharomyces cerevisiae TOP3 gene encodes the type IA topoisomerase (Top3p) that is highly conserved in evolution...
  30. Mankouri H, Ashton T, Hickson I. Holliday junction-containing DNA structures persist in cells lacking Sgs1 or Top3 following exposure to DNA damage. Proc Natl Acad Sci U S A. 2011;108:4944-9 pubmed publisher
    The Sgs1-Rmi1-Top3 "dissolvasome" is required for the maintenance of genome stability and has been implicated in the processing of various types of DNA structures arising during DNA replication...
  31. Tang S, Wu M, Zhang R, Hunter N. Pervasive and essential roles of the Top3-Rmi1 decatenase orchestrate recombination and facilitate chromosome segregation in meiosis. Mol Cell. 2015;57:607-21 pubmed publisher
    ..Sgs1 can associate with type-I topoisomerase Top3 and its accessory factor Rmi1 to form a conserved complex best known for its unique ability to decatenate double-..
  32. Weinstein J, Rothstein R. The genetic consequences of ablating helicase activity and the Top3 interaction domain of Sgs1. DNA Repair (Amst). 2008;7:558-71 pubmed publisher
    Sgs1, the RecQ helicase homolog, and Top3, the type-IA topoisomerase, physically interact and are required for genomic stability in budding yeast...
  33. Glineburg M, Chavez A, Agrawal V, Brill S, Johnson F. Resolution by unassisted Top3 points to template switch recombination intermediates during DNA replication. J Biol Chem. 2013;288:33193-204 pubmed publisher
    The evolutionarily conserved Sgs1/Top3/Rmi1 (STR) complex plays vital roles in DNA replication and repair...
  34. Gadal O, Labarre S, Boschiero C, Thuriaux P. Hmo1, an HMG-box protein, belongs to the yeast ribosomal DNA transcription system. EMBO J. 2002;21:5498-507 pubmed
    ..As an HMG-box protein, Hmo1 is remotely related to animal UBF factors. hmo1-Delta and rpa49-Delta are lethal with top3-Delta DNA topoisomerase (type I) mutants and are suppressed in mutants lacking the Sgs1 DNA helicase...
  35. Mankouri H, Hickson I. Top3 processes recombination intermediates and modulates checkpoint activity after DNA damage. Mol Biol Cell. 2006;17:4473-83 pubmed
    Mutation of TOP3 in Saccharomyces cerevisiae causes poor growth, hyperrecombination, and a failure to fully activate DNA damage checkpoints in S phase...
  36. Onodera R, Seki M, Ui A, Satoh Y, Miyajima A, Onoda F, et al. Functional and physical interaction between Sgs1 and Top3 and Sgs1-independent function of Top3 in DNA recombination repair. Genes Genet Syst. 2002;77:11-21 pubmed
    A mutant allele of SGS1 of Saccharomyces cerevisiae was identified as a suppressor of the slow-growth phenotype of top3 mutants...
  37. Allen Soltero S, Martinez S, Putnam C, Kolodner R. A saccharomyces cerevisiae RNase H2 interaction network functions to suppress genome instability. Mol Cell Biol. 2014;34:1521-34 pubmed publisher
    ..This analysis suggests that cells with RNase H2 defects have increased levels of DNA damage and depend on other pathways of DNA metabolism to overcome the deleterious effects of this DNA damage. ..
  38. Saffi J, Feldmann H, Winnacker E, Henriques J. Interaction of the yeast Pso5/Rad16 and Sgs1 proteins: influences on DNA repair and aging. Mutat Res. 2001;486:195-206 pubmed
    ..Moreover, we found that in a top3 background, functional Sgs1p and Rad16p apparently channel MMS, 4-NQO and H2O2 induced lesions into aberrant DNA ..
  39. O Neill B, Hanway D, Winzeler E, Romesberg F. Coordinated functions of WSS1, PSY2 and TOF1 in the DNA damage response. Nucleic Acids Res. 2004;32:6519-30 pubmed
    ..WSS1 was also found to interact genetically with SGS1, TOP3, SRS2 and CTF4, which are involved in recombination, repair of replication forks and the establishment of sister ..
  40. Matulova P, Marini V, Burgess R, Sisakova A, Kwon Y, Rothstein R, et al. Cooperativity of Mus81.Mms4 with Rad54 in the resolution of recombination and replication intermediates. J Biol Chem. 2009;284:7733-45 pubmed publisher
    ..b>Top3. These findings provide functional insights into the biological importance of the higher order complex of Mus81...
  41. Tsai H, Huang W, Li T, Tsai Y, Wu K, Tseng S, et al. Involvement of topoisomerase III in telomere-telomere recombination. J Biol Chem. 2006;281:13717-23 pubmed
    ..Moreover, the RIF1 and RIF2 genes are required for the establishment of TOP3/SGS1-dependent telomere-telomere recombination...
  42. Fasching C, Cejka P, Kowalczykowski S, Heyer W. Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism. Mol Cell. 2015;57:595-606 pubmed publisher
    ..Here we report that D loops can also be disrupted by DNA topoisomerase 3 (Top3), and this disruption depends on Top3's catalytic activity...
  43. Mundbjerg K, Jørgensen S, Fredsøe J, Nielsen I, Pedersen J, Bentsen I, et al. Top2 and Sgs1-Top3 Act Redundantly to Ensure rDNA Replication Termination. PLoS Genet. 2015;11:e1005697 pubmed publisher
    ..We find that cells lacking Top2 and Sgs1 (or Top3) display two different characteristics during late S/G2 phase, checkpoint activation and accumulation of asymmetric ..
  44. Kim R, Wang J. Identification of the yeast TOP3 gene product as a single strand-specific DNA topoisomerase. J Biol Chem. 1992;267:17178-85 pubmed
    The TOP3 gene of the yeast Saccharomyces cerevisiae was postulated to encode a DNA topoisomerase, based on its sequence homology to Escherichia coli DNA topoisomerase I and the suppression of the poor growth phenotype of top3 mutants by ..
  45. Ui A, Satoh Y, Onoda F, Miyajima A, Seki M, Enomoto T. The N-terminal region of Sgs1, which interacts with Top3, is required for complementation of MMS sensitivity and suppression of hyper-recombination in sgs1 disruptants. Mol Genet Genomics. 2001;265:837-50 pubmed
    ..MMS sensitivity and suppress hyper-recombination in sgs1 mutants, and also prevented its interaction with Top3, indicating that interaction with Top3 via the N-terminal region of Sgs1 is involved in the complementation of MMS ..
  46. Cejka P, Plank J, Dombrowski C, Kowalczykowski S. Decatenation of DNA by the S. cerevisiae Sgs1-Top3-Rmi1 and RPA complex: a mechanism for disentangling chromosomes. Mol Cell. 2012;47:886-96 pubmed publisher
    Genetic evidence indicates that Saccharomyces cerevisiae Sgs1, Top3, and Rmi1 resolve topologically linked intermediates arising from DNA replication and recombination...
  47. Bernstein K, Juanchich A, Sunjevaric I, Rothstein R. The Shu complex regulates Rad52 localization during rDNA repair. DNA Repair (Amst). 2013;12:786-90 pubmed publisher
    ..Our results suggest that in the absence of UAF30, the Shu complex plays a central role in Rad52 rDNA localization as long as Rad52 can be sumoylated. This discrimination is important for rDNA copy number homeostasis. ..
  48. Barker C, Mouchel N, Jenkins J. The identification and characterisation of a functional interaction between arginyl-tRNA-protein transferase and topoisomerase II. Biochem Biophys Res Commun. 2006;342:596-604 pubmed
    ..Ate1 is a component of the N-end rule protein degradation pathway which targets proteins for degradation. We also propose a previously unidentified role for Ate1 in modulating the level of topoisomerase II through the cell cycle. ..
  49. Klein H. Mutations in recombinational repair and in checkpoint control genes suppress the lethal combination of srs2Delta with other DNA repair genes in Saccharomyces cerevisiae. Genetics. 2001;157:557-65 pubmed
    ..However, cells do not achieve wild-type growth rates, suggesting that unrepaired damage is still present and may lead to chromosome loss. ..
  50. Dunø M, Thomsen B, Westergaard O, Krejci L, Bendixen C. Genetic analysis of the Saccharomyces cerevisiae Sgs1 helicase defines an essential function for the Sgs1-Top3 complex in the absence of SRS2 or TOP1. Mol Gen Genet. 2000;264:89-97 pubmed
    ..and demonstrate that the complex phenotypes associated with sgs1 mutants are a consequence of a dysfunctional Sgs1-Top3 complex...
  51. 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
  52. Mullen J, Kaliraman V, Brill S. Bipartite structure of the SGS1 DNA helicase in Saccharomyces cerevisiae. Genetics. 2000;154:1101-14 pubmed
    ..MMS hypersensitivity and hyper-recombination phenotypes, but partially complemented the slow-growth suppression of top3 sgs1 strains and the top1 sgs1 growth defect...