TOP2

Summary

Gene Symbol: TOP2
Description: DNA topoisomerase 2
Alias: TOR3, TRF3, DNA topoisomerase 2
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Furniss K, Tsai H, Byl J, Lane A, Vas A, Hsu W, et al. Direct monitoring of the strand passage reaction of DNA topoisomerase II triggers checkpoint activation. PLoS Genet. 2013;9:e1003832 pubmed publisher
    ..In contrast, we have described the first example of a distinct category of checkpoint mechanism that monitors the catalytic cycle of a single specific enzyme in order to determine when chromosome segregation can proceed faithfully. ..
  2. Fernandez X, Díaz Ingelmo O, Martínez García B, Roca J. Chromatin regulates DNA torsional energy via topoisomerase II-mediated relaxation of positive supercoils. EMBO J. 2014;33:1492-501 pubmed publisher
  3. Fachinetti D, Bermejo R, Cocito A, Minardi S, Katou Y, Kanoh Y, et al. Replication termination at eukaryotic chromosomes is mediated by Top2 and occurs at genomic loci containing pausing elements. Mol Cell. 2010;39:595-605 pubmed publisher
    ..The Top2 DNA topoisomerase associates at TERs in S phase, and G2/M facilitates fork fusion and prevents DNA breaks and ..
  4. Kim R, Wang J. Function of DNA topoisomerases as replication swivels in Saccharomyces cerevisiae. J Mol Biol. 1989;208:257-67 pubmed
    ..I and II in DNA replication by the use of a set of four isogenic strains of Saccharomyces cerevisiae that are TOP1+ TOP2+, TOP1+ top2 ts, delta top1 TOP2+, and delta top1 top2 ts...
  5. Andrews C, Vas A, Meier B, Giménez Abián J, Diaz Martinez L, Green J, et al. A mitotic topoisomerase II checkpoint in budding yeast is required for genome stability but acts independently of Pds1/securin. Genes Dev. 2006;20:1162-74 pubmed
    ..Thus, compromised Topo II function activates a yeast checkpoint system that operates by a novel mechanism. ..
  6. Sperling A, Jeong K, Kitada T, Grunstein M. Topoisomerase II binds nucleosome-free DNA and acts redundantly with topoisomerase I to enhance recruitment of RNA Pol II in budding yeast. Proc Natl Acad Sci U S A. 2011;108:12693-8 pubmed publisher
    ..we present high-resolution genome-wide maps of one of the major eukaryotic topoisomerases, Topoisomerase II (Top2) and nucleosomes in the budding yeast, Saccharomyces cerevisiae...
  7. Takahashi Y, Yong Gonzalez V, Kikuchi Y, Strunnikov A. SIZ1/SIZ2 control of chromosome transmission fidelity is mediated by the sumoylation of topoisomerase II. Genetics. 2006;172:783-94 pubmed
    ..By combining mutations in the TOP2 sumoylation sites and the SIZ1 and SIZ2 genes we demonstrate that the minichromosome segregation defect and ..
  8. 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
  9. D Ambrosio C, Kelly G, Shirahige K, Uhlmann F. Condensin-dependent rDNA decatenation introduces a temporal pattern to chromosome segregation. Curr Biol. 2008;18:1084-9 pubmed publisher
    ..Regulation of decatenation therefore provides a means to fine tune the segregation timing of chromosomes in mitosis. ..

More Information

Publications62

  1. Christman M, Dietrich F, Fink G. Mitotic recombination in the rDNA of S. cerevisiae is suppressed by the combined action of DNA topoisomerases I and II. Cell. 1988;55:413-25 pubmed
    ..Strains with a null mutation in the TOP1 gene (encoding topoisomerase I) or a ts mutation in the TOP2 gene (encoding topoisomerase II) grown at a semipermissive temperature show 50- to 200-fold higher frequencies of ..
  2. Charbin A, Bouchoux C, Uhlmann F. Condensin aids sister chromatid decatenation by topoisomerase II. Nucleic Acids Res. 2014;42:340-8 pubmed publisher
    ..Our results provide evidence that condensin prevents deleterious anaphase bridges during chromosome segregation by promoting sister chromatid decatenation. ..
  3. Salceda J, Fernandez X, Roca J. Topoisomerase II, not topoisomerase I, is the proficient relaxase of nucleosomal DNA. EMBO J. 2006;25:2575-83 pubmed
    ..We conclude that topoisomerase II is the main modulator of DNA topology in chromatin fibers. The nonessential topoisomerase I then assists DNA relaxation where chromatin structure impairs DNA juxtaposition but allows twist diffusion. ..
  4. Baxter J, Sen N, Martínez V, De Carandini M, Schvartzman J, Diffley J, et al. Positive supercoiling of mitotic DNA drives decatenation by topoisomerase II in eukaryotes. Science. 2011;331:1328-32 pubmed publisher
    ..Thus, a topological change on DNA drives topoisomerase II to decatenate molecules during mitosis, potentially driving the full decatenation of the genome. ..
  5. Warsi T, Navarro M, Bachant J. DNA topoisomerase II is a determinant of the tensile properties of yeast centromeric chromatin and the tension checkpoint. Mol Biol Cell. 2008;19:4421-33 pubmed publisher
    ..Here, we report observations linking yeast Topoisomerase II (Top2) to both CEN mechanics and assessment of interkinetochore tension...
  6. Bermejo R, Doksani Y, Capra T, Katou Y, Tanaka H, Shirahige K, et al. Top1- and Top2-mediated topological transitions at replication forks ensure fork progression and stability and prevent DNA damage checkpoint activation. Genes Dev. 2007;21:1921-36 pubmed
    DNA topoisomerases solve topological problems during chromosome metabolism. We investigated where and when Top1 and Top2 are recruited on replicating chromosomes and how their inactivation affects fork integrity and DNA damage checkpoint ..
  7. Trigueros S, Roca J. Failure to relax negative supercoiling of DNA is a primary cause of mitotic hyper-recombination in topoisomerase-deficient yeast cells. J Biol Chem. 2002;277:37207-11 pubmed
    ..Yeast Delta top1 top2(ts) mutants grow slowly and present structural instability in the genome; over half of the rDNA repeats are excised ..
  8. Garinther W, Schultz M. Topoisomerase function during replication-independent chromatin assembly in yeast. Mol Cell Biol. 1997;17:3520-6 pubmed
    ..from a yeast mutant with no topoisomerase I and a temperature-sensitive form of topoisomerase II (strain top1-top2)...
  9. Joshi R, Pina B, Roca J. Topoisomerase II is required for the production of long Pol II gene transcripts in yeast. Nucleic Acids Res. 2012;40:7907-15 pubmed publisher
    ..Apparently, only topo II relaxes efficiently the (+) DNA supercoils that stall the advancement of Pol II in long genes. A mechanistic model is proposed. ..
  10. El Hage A, French S, Beyer A, Tollervey D. Loss of Topoisomerase I leads to R-loop-mediated transcriptional blocks during ribosomal RNA synthesis. Genes Dev. 2010;24:1546-58 pubmed publisher
    ..Loss of both Top1 and Top2 blocked pre-rRNA synthesis, with pre-rRNAs truncated predominately in the 18S 5' region...
  11. Fass D, Bogden C, Berger J. Quaternary changes in topoisomerase II may direct orthogonal movement of two DNA strands. Nat Struct Biol. 1999;6:322-6 pubmed
  12. Bachant J, Alcasabas A, Blat Y, Kleckner N, Elledge S. The SUMO-1 isopeptidase Smt4 is linked to centromeric cohesion through SUMO-1 modification of DNA topoisomerase II. Mol Cell. 2002;9:1169-82 pubmed
    ..control chromosome cohesion at centromeric regions and that a key Smt3/SUMO-1 substrate underlying this function is Top2, DNA Topoisomerase II...
  13. Schmidt B, Burgin A, Deweese J, Osheroff N, Berger J. A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases. Nature. 2010;465:641-4 pubmed publisher
    ..This connection illustrates how an indispensable chromosome-disentangling machine auto-regulates DNA breakage to prevent the aberrant formation of mutagenic and cytotoxic genomic lesions. ..
  14. Bermejo R, Capra T, Gonzalez Huici V, Fachinetti D, Cocito A, Natoli G, et al. Genome-organizing factors Top2 and Hmo1 prevent chromosome fragility at sites of S phase transcription. Cell. 2009;138:870-84 pubmed publisher
    ..We have investigated the contribution of Top2 in S phase transcription. Specifically in S phase, Top2 binds intergenic regions close to transcribed genes...
  15. Goto T, Laipis P, Wang J. The purification and characterization of DNA topoisomerases I and II of the yeast Saccharomyces cerevisiae. J Biol Chem. 1984;259:10422-9 pubmed
    ..In addition, the type II enzyme, but not the type I enzyme, is inhibited to various extents by coumermycin, ethidium, and berenil. Both topoisomerases are nuclear enzymes; no topoisomerase specific to mitochondria has been detected. ..
  16. Dong K, Berger J. Structural basis for gate-DNA recognition and bending by type IIA topoisomerases. Nature. 2007;450:1201-5 pubmed
    ..structure of a complex between the DNA-binding and cleavage core of Saccharomyces cerevisiae Topo II (also known as Top2) and a gate-DNA segment...
  17. García Rubio M, Aguilera A. Topological constraints impair RNA polymerase II transcription and causes instability of plasmid-borne convergent genes. Nucleic Acids Res. 2012;40:1050-64 pubmed publisher
    ..Our work shows that topological constraints negatively affect RNAPII transcription and genetic integrity, and provides an assay to study gene regulation by transcription interference. ..
  18. Takahashi Y, Strunnikov A. In vivo modeling of polysumoylation uncovers targeting of Topoisomerase II to the nucleolus via optimal level of SUMO modification. Chromosoma. 2008;117:189-98 pubmed
    ..Further analysis has established that poly-sumoylation of Top2p is required for the stable maintenance of the nucleolar organizer, linking SUMO-mediated targeting to functional maintenance of ribosomal RNA gene cluster. ..
  19. Watt P, Louis E, Borts R, Hickson I. Sgs1: a eukaryotic homolog of E. coli RecQ that interacts with topoisomerase II in vivo and is required for faithful chromosome segregation. Cell. 1995;81:253-60 pubmed
    ..We propose a model to account for the interaction of a topoisomerase and a helicase in the faithful segregation of newly replicated eukaryotic chromosomes. ..
  20. Goto T, Wang J. Yeast DNA topoisomerase II is encoded by a single-copy, essential gene. Cell. 1984;36:1073-80 pubmed
    The gene TOP2 encoding yeast topoisomerase II has been cloned by immunological screening of a yeast genomic library constructed in the phage lambda expression vector, lambda gt11...
  21. Amaral N, Vendrell A, Funaya C, Idrissi F, Maier M, Kumar A, et al. The Aurora-B-dependent NoCut checkpoint prevents damage of anaphase bridges after DNA replication stress. Nat Cell Biol. 2016;18:516-26 pubmed publisher
    ..Therefore, the molecular origin of chromatin bridges is critical for activation of NoCut, which plays a key role in the maintenance of genome stability after replicative stress. ..
  22. D Ambrosio L, Lavoie B. Pds5 prevents the PolySUMO-dependent separation of sister chromatids. Curr Biol. 2014;24:361-71 pubmed publisher
    ..We propose that Pds5 maintains cohesion, at least in part, by antagonizing the polySUMO-dependent degradation of cohesin. ..
  23. Sadoff B, Heath Pagliuso S, Castaño I, Zhu Y, Kieff F, Christman M. Isolation of mutants of Saccharomyces cerevisiae requiring DNA topoisomerase I. Genetics. 1995;141:465-79 pubmed
    ..The TRF genes define at least four complementation groups. TRF3 is allelic to TOP2. TRF1 is allelic to HPR1, previously shown to be homologous to TOP1 over two short regions...
  24. Titos I, Ivanova T, Mendoza M. Chromosome length and perinuclear attachment constrain resolution of DNA intertwines. J Cell Biol. 2014;206:719-33 pubmed publisher
    ..We propose that topological constraints imposed by chromosome length and perinuclear attachment determine the amount of SCI that topo II and dynamic microtubules resolve during anaphase. ..
  25. Takahashi Y, Dulev S, Liu X, Hiller N, Zhao X, Strunnikov A. Cooperation of sumoylated chromosomal proteins in rDNA maintenance. PLoS Genet. 2008;4:e1000215 pubmed publisher
    ..In addition, binding of cohesin and condensin to rDNA is altered in the mms21-CH E3-deficient mutant. ..
  26. Klein F, Laroche T, Cardenas M, Hofmann J, Schweizer D, Gasser S. Localization of RAP1 and topoisomerase II in nuclei and meiotic chromosomes of yeast. J Cell Biol. 1992;117:935-48 pubmed
    ..Approximately 16 brightly staining foci can be identified in a diploid nucleus stained with anti-RAP1 antibodies, suggesting that telomeres are grouped together, perhaps through interaction with the nuclear envelope. ..
  27. Gonzalez Huici V, Szakal B, Urulangodi M, Psakhye I, Castellucci F, Menolfi D, et al. DNA bending facilitates the error-free DNA damage tolerance pathway and upholds genome integrity. EMBO J. 2014;33:327-40 pubmed publisher
    ..Together, the results suggest that replication-associated topological changes involving the molecular DNA bender, Hmo1, set the stage for dedicated repair reactions that limit errors during replication and impact on genome stability. ..
  28. Zhang L, Wang S, Yin S, Hong S, Kim K, Kleckner N. Topoisomerase II mediates meiotic crossover interference. Nature. 2014;511:551-6 pubmed publisher
  29. Trigueros S, Roca J. Circular minichromosomes become highly recombinogenic in topoisomerase-deficient yeast cells. J Biol Chem. 2001;276:2243-8 pubmed
    ..This phenomenon selectively occurs in Deltatop1 cells, and is highly magnified in double mutant Deltatop1 top2-4 cells...
  30. 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
    ..Our findings indicate that Sgs1 may act on different DNA structures depending on the activity of topoisomerase I, Srs2 and topoisomerase III. ..
  31. Park H, Sternglanz R. Two separate conserved domains of eukaryotic DNA topoisomerase I bind to each other and reconstitute enzymatic activity. Chromosoma. 1998;107:211-5 pubmed
    ..The results demonstrate that the central domain of topoisomerase I interacts with the C-terminal domain of the protein and that these two domains reconstitute enzymatic activity in vivo, even when expressed as separate polypeptides. ..
  32. Tackett A, Dilworth D, Davey M, O DONNELL M, Aitchison J, Rout M, et al. Proteomic and genomic characterization of chromatin complexes at a boundary. J Cell Biol. 2005;169:35-47 pubmed
    ..The complexes consist of at least 15 chromatin-associated proteins, including DNA pol epsilon, the Isw2-Itc1 and Top2 chromatin remodeling proteins, the Sas3-Spt16 chromatin modifying complex, and Yta7, a bromodomain-containing AAA ..
  33. Sabourin M, Nitiss J, Nitiss K, Tatebayashi K, Ikeda H, Osheroff N. Yeast recombination pathways triggered by topoisomerase II-mediated DNA breaks. Nucleic Acids Res. 2003;31:4373-84 pubmed
    ..Non-homologous end joining also was triggered by etoposide treatment, but this pathway was considerably less active than single-strand invasion and did not contribute significantly to cell survival in S.cerevisiae. ..
  34. Murillo Pineda M, Cabello Lobato M, Clemente Ruiz M, Monje Casas F, Prado F. Defective histone supply causes condensin-dependent chromatin alterations, SAC activation and chromosome decatenation impairment. Nucleic Acids Res. 2014;42:12469-82 pubmed publisher
    ..In particular, Top2 and condensin are directly involved in both the resolution of precatenanes that form during replication and the ..
  35. Lamhasni S, Larsen A, Barray M, Monnot M, Delain E, Fermandjian S. Changes of self-association, secondary structure, and biological activity properties of topoisomerase II under varying salt conditions. Biochemistry. 1995;34:3632-9 pubmed
    ..Second, circular dichroism (CD) showed the sensitivity of the topoisomerase II secondary structure to salt concentration, the observed variations being apparently dependent upon the ionic strength.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  36. Pedersen J, Fredsoe J, Roedgaard M, Andreasen L, Mundbjerg K, Kruhøffer M, et al. DNA Topoisomerases maintain promoters in a state competent for transcriptional activation in Saccharomyces cerevisiae. PLoS Genet. 2012;8:e1003128 pubmed publisher
    ..In conclusion, our results reveal a hitherto unknown function of topoisomerases during transcriptional activation of genes with a repressible/inducible mode of regulation. ..
  37. Hashash N, Johnson A, Cha R. Topoisomerase II- and condensin-dependent breakage of MEC1ATR-sensitive fragile sites occurs independently of spindle tension, anaphase, or cytokinesis. PLoS Genet. 2012;8:e1002978 pubmed publisher
    ..RSZ breakage, however, required genes encoding condensin subunits (YCG1, YSC4) and topoisomerase II (TOP2)...
  38. Sen N, Leonard J, Torres R, Garcia Luis J, Palou Marin G, Aragon L. Physical Proximity of Sister Chromatids Promotes Top2-Dependent Intertwining. Mol Cell. 2016;64:134-147 pubmed publisher
    ..DNA replication, and their removal is thought to occur because of the intrinsic feature of type II topoisomerases (Top2) to simplify DNA topology...
  39. Rogojina A, Nitiss J. Isolation and characterization of mAMSA-hypersensitive mutants. Cytotoxicity of Top2 covalent complexes containing DNA single strand breaks. J Biol Chem. 2008;283:29239-50 pubmed publisher
    Topoisomerase II (Top2) is the primary target for active anti-cancer agents...
  40. Nitiss K, Malik M, He X, White S, Nitiss J. Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage. Proc Natl Acad Sci U S A. 2006;103:8953-8 pubmed
    ..We found that deletion of the TDP1 gene in yeast confers hypersensitivity to Top2 targeting agents...
  41. Schmidt B, Osheroff N, Berger J. Structure of a topoisomerase II-DNA-nucleotide complex reveals a new control mechanism for ATPase activity. Nat Struct Mol Biol. 2012;19:1147-54 pubmed publisher
    ..Our data indicate that the ATPase domains pivot about each other to ensure unidirectional strand passage and that this state senses bound DNA to promote ATP turnover and enzyme reset. ..
  42. Wang X, Watt P, Louis E, Borts R, Hickson I. Pat1: a topoisomerase II-associated protein required for faithful chromosome transmission in Saccharomyces cerevisiae. Nucleic Acids Res. 1996;24:4791-7 pubmed
    Saccharomyces cerevisiae top2 mutants deficient in topoisomerase II activity are defective in chromosome segregation during both mitotic and meiotic cell divisions...
  43. El Hage A, Webb S, Kerr A, Tollervey D. Genome-wide distribution of RNA-DNA hybrids identifies RNase H targets in tRNA genes, retrotransposons and mitochondria. PLoS Genet. 2014;10:e1004716 pubmed publisher
    ..Finally, R-loops were detected on actively transcribed protein-coding genes in the wild-type, particularly over the second exon of spliced ribosomal protein genes. ..
  44. Kanno T, Berta D, Sjögren C. The Smc5/6 Complex Is an ATP-Dependent Intermolecular DNA Linker. Cell Rep. 2015;12:1471-82 pubmed publisher
    ..Taken together, these results indicate that Smc5/6 executes its cellular functions through ATP-regulated intermolecular DNA linking. ..
  45. Mueller Planitz F, Herschlag D. Coupling between ATP binding and DNA cleavage by DNA topoisomerase II: A unifying kinetic and structural mechanism. J Biol Chem. 2008;283:17463-76 pubmed publisher
  46. Chiroli E, Rossio V, Lucchini G, Piatti S. The budding yeast PP2ACdc55 protein phosphatase prevents the onset of anaphase in response to morphogenetic defects. J Cell Biol. 2007;177:599-611 pubmed
    ..We find that the protein phosphatase PP2A bound to its regulatory subunit Cdc55 plays a key role in this process, uncovering a new function for PP2A(Cdc55) in controlling a noncanonical pathway of chromatid cohesion removal. ..
  47. Aguilar C, Davidson C, Dix M, Stead K, Zheng K, Hartman T, et al. Topoisomerase II suppresses the temperature sensitivity of Saccharomyces cerevisiae pds5 mutants, but not the defect in sister chromatid cohesion. Cell Cycle. 2005;4:1294-304 pubmed
    ..We identified TOP2 as a high-copy suppressor of the temperature sensitivity of pds5 mutants...
  48. Benedetti P, Silvestri A, Fiorani P, Wang J. Study of yeast DNA topoisomerase II and its truncation derivatives by transmission electron microscopy. J Biol Chem. 1997;272:12132-7 pubmed
  49. Vassetzky Y, Dang Q, Benedetti P, Gasser S. Topoisomerase II forms multimers in vitro: effects of metals, beta-glycerophosphate, and phosphorylation of its C-terminal domain. Mol Cell Biol. 1994;14:6962-74 pubmed
    ..This is consistent with a model in which interactions involving the phosphorylated C-terminal domain of topoisomerase II aid either in chromosome segregation or in chromosome condensation. ..
  50. Rose D, Thomas W, Holm C. Segregation of recombined chromosomes in meiosis I requires DNA topoisomerase II. Cell. 1990;60:1009-17 pubmed
    ..In meiosis, we found that topoisomerase II is required only at the time of nuclear division. When cold-sensitive top2 mutants are induced to sporulate at the restrictive temperature, they undergo premeiotic DNA synthesis and ..
  51. Mouchel N, Jenkins J. The identification of a functional interaction between PKC and topoisomerase II. FEBS Lett. 2006;580:51-7 pubmed
    ..cerevisiae topoisomerase II. The S. cerevisiae Pkc1 is the homologue of the mammalian calcium dependent PKC. ..
  52. Jeppsson K, Carlborg K, Nakato R, Berta D, Lilienthal I, Kanno T, et al. The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement. PLoS Genet. 2014;10:e1004680 pubmed publisher
    ..and chromosome segregation, also inhibits resolution of sister chromatid intertwinings (SCIs) by the topoisomerase Top2. The cohesin-related Smc5/6 complex (Smc5/6) instead accumulates on chromosomes after Top2 inactivation, known to ..
  53. 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
    ..Here we have investigated the potential roles of Topoisomerase II (Top2) and the RecQ helicase Sgs1 during late stages of replication...