General Information
Symbol
Dmel\Top2
Species
D. melanogaster
Name
Topoisomerase 2
Annotation Symbol
CG10223
Feature Type
FlyBase ID
FBgn0284220
Gene Model Status
Stock Availability
Enzyme Name (EC)
DNA topoisomerase (ATP-hydrolyzing) (5.99.1.3)
Gene Snapshot
Topoisomerase 2 is an enzyme that alters the topology of DNA by creating a transient DNA double strand breakage. It is essential for removing supercoils generated via DNA replication and transcription, and decatenating replicated sister chromosomes during cell division. [Date last reviewed: 2016-06-23]
Also Known As
topo II, TopoII, CHRAC, suo, dCHRAC
Genomic Location
Cytogenetic map
Sequence location
2L:19,447,365..19,453,490 [-]
Recombination map
2-54
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
GO Summary Ribbons
Families, Domains and Molecular Function
Gene Group Membership (FlyBase)
Protein Family (UniProt, Sequence Similarities)
Belongs to the type II topoisomerase family. (P15348)
Catalytic Activity (EC)
Experimental Evidence
ATP-dependent breakage, passage and rejoining of double-stranded DNA (5.99.1.3)
Predictions / Assertions
-
Summaries
Gene Group Membership
DNA TOPOISOMERASES -
DNA topoisomerases perform topological transformations of DNA by generating a transient DNA break through which strand passage can occur. These enzymes are grouped into types I and II based on structure and mechanism: type I enzymes carry out strand passage through a reversible single-strand break, whereas type II enzymes mediate strand transport through a double-strand DNA gate. DNA topoisomerases have critical roles in DNA replication, transcription, recombination, repair, and chromatin remodeling. (Adapted from PMID:23495937.)
UniProt Contributed Function Data
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands (PubMed:6308011, PubMed:2547764, PubMed:1328202, PubMed:8383533, PubMed:10786800, PubMed:8978614). Topoisomerase II makes double-strand breaks (PubMed:6308011, PubMed:2547764, PubMed:1328202, PubMed:8383533, PubMed:10786800, PubMed:9545289). Essential during mitosis and meiosis for proper segregation of daughter chromosomes (PubMed:10751154, PubMed:14600258, PubMed:18752348, PubMed:25340780). During meiosis, it disrupts heterochromatic connections between achiasmate and chiasmate homologs after spindle assembly so that chromosomes can separate at prometaphase I (PubMed:25340780). During mitosis, it functions in the separation of sister chromatids by establishing amphitelic kinetochore attachments in mitotic spindles (PubMed:18752348). May have a role in chromatin condensation and chromosome structure (PubMed:14600258, PubMed:18752348, PubMed:25340780). May be involved in X-chromosome dosage compensation, perhaps by modifying the topological state of compensated genes (PubMed:23989663). Regulates activity of the gypsy chromatin insulator complex by binding to mod(mdg4) and preventing its degradation (PubMed:21304601).
(UniProt, P15348)
Phenotypic Description from the Red Book (Lindsley and Zimm 1992)
Top2: Topoisomerase 2
Top2 is an essential gene that encodes the large subunit of type II DNA topoisomerase, an enzyme believed to play an important role in the condensation, decondensation, and segregation of chromosomes. The enzyme is a major component of the nuclear matrix of Drosophila cells (Berrios et al., 1985) and is distributed along polytene chromosomes paralleling the distribution of the DNA (Heller et al., 1986). It is believed to act by passing a DNA segment through a transient double-stranded break in another segment. Major cleavage sites for type II topisomerase have been found in nontranscribed spacer segments and in the 5' and 3' ends of Hsp70 and the histone genes (Udvardy et al., 1985). When prepared from embryos, the purified enzyme is made up of a major polypeptide encoded by Top2 of 166,000 daltons, with binding sites for both DNA and ATP, and, in addition, smaller polypeptides of 30,000-40,000 and 132,000-145,000 daltons (Sander and Hsieh, 1983; Shelton et al., 1983; Heller et al., 1986). Protein kinase activity is associated with Drosophila topoisomerase II (Sander et al., 1984; Ackerman, Glover, and Osheroff, 1985, Proc. Nat. Acad. Sci. USA 82: 3164-68).
Gene Model and Products
Number of Transcripts
2
Number of Unique Polypeptides
1

Please see the GBrowse view of Dmel\Top2 or the JBrowse view of Dmel\Top2 for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Comments on Gene Model
Annotated transcripts do not represent all supported alternative splices within 5' UTR.
Gene model reviewed during 5.45
Gene model reviewed during 5.55
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0081287
4934
1447
FBtr0332320
5242
1447
Additional Transcript Data and Comments
Reported size (kB)
5.1 (northern blot)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0080825
164.4
1447
8.45
FBpp0304598
164.4
1447
8.45
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

1447 aa isoforms: Top2-PA, Top2-PB
Additional Polypeptide Data and Comments
Reported size (kDa)
1447 (aa); 164.424 (kD predicted)
170 (kD predicted)
Comments
External Data
Subunit Structure (UniProtKB)
Homodimer (By similarity). Interacts with mod(mdg4) (PubMed:21304601). Interacts with barr (PubMed:8978614, PubMed:11172718). Interacts with ph-p (PubMed:11172718). Interacts with mle; the interaction mediates association with the MSL dosage compensation complex (PubMed:23989663).
(UniProt, P15348)
Post Translational Modification
Phosphorylated (PubMed:1328202, PubMed:8383533, PubMed:10751154). Phosphorylation by casein kinase II enhances ATPase activity (PubMed:1328202).
(UniProt, P15348)
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Top2 using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Gene Ontology (24 terms)
Molecular Function (9 terms)
Terms Based on Experimental Evidence (8 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
Biological Process (10 terms)
Terms Based on Experimental Evidence (9 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
traceable author statement
traceable author statement
Cellular Component (5 terms)
Terms Based on Experimental Evidence (5 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
NOT CHRAC
inferred from direct assay
inferred from direct assay
colocalizes_with condensed chromosome
inferred from direct assay
Terms Based on Predictions or Assertions (0 terms)
Expression Data
Transcript Expression
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
NOT CHRAC
inferred from direct assay
inferred from direct assay
colocalizes_with condensed chromosome
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\Top2 in GBrowse 2
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
Images
Alleles, Insertions, Transgenic Constructs and Phenotypes
Classical and Insertion Alleles ( 26 )
For All Classical and Insertion Alleles Show
 
Allele of Top2
Class
Mutagen
Associated Insertion
Stocks
Known lesion
Other relevant insertions
Transgenic Constructs ( 6 )
Deletions and Duplications ( 6 )
Summary of Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
chromosome | male (with Top2suo1)
chromosome | male (with Top2suo3)
metaphase & condensed nuclear chromosome
metaphase & condensed nuclear chromosome & spermatocyte
Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (2)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
14 of 15
Yes
Yes
12 of 15
No
Yes
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (2)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
15 of 15
Yes
Yes
12 of 15
No
Yes
Rattus norvegicus (Norway rat) (2)
8 of 13
Yes
Yes
1 of 13
No
Yes
Xenopus tropicalis (Western clawed frog) (2)
7 of 12
Yes
Yes
6 of 12
No
Yes
Danio rerio (Zebrafish) (2)
13 of 15
Yes
Yes
10 of 15
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (3)
15 of 15
Yes
Yes
7 of 15
No
Yes
6 of 15
No
Yes
Arabidopsis thaliana (thale-cress) (1)
8 of 9
Yes
Yes
Saccharomyces cerevisiae (Brewer's yeast) (1)
14 of 15
Yes
Yes
Schizosaccharomyces pombe (Fission yeast) (1)
11 of 12
Yes
Yes
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG091900SW )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila sechellia
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG091500O2 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Lucilia cuprina
Australian sheep blowfly
Mayetiola destructor
Hessian fly
Aedes aegypti
Yellow fever mosquito
Anopheles darlingi
American malaria mosquito
Anopheles gambiae
Malaria mosquito
Culex quinquefasciatus
Southern house mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W00YW )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Apis florea
Little honeybee
Apis mellifera
Western honey bee
Bombus impatiens
Common eastern bumble bee
Bombus terrestris
Buff-tailed bumblebee
Linepithema humile
Argentine ant
Megachile rotundata
Alfalfa leafcutting bee
Nasonia vitripennis
Parasitic wasp
Dendroctonus ponderosae
Mountain pine beetle
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X00GT )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
Strigamia maritima
European centipede
Ixodes scapularis
Black-legged tick
Stegodyphus mimosarum
African social velvet spider
Tetranychus urticae
Two-spotted spider mite
Tetranychus urticae
Two-spotted spider mite
Tetranychus urticae
Two-spotted spider mite
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G00U2 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Ciona intestinalis
Vase tunicate
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Human Disease Model Data
FlyBase Human Disease Model Reports
    Alleles Reported to Model Human Disease (Disease Ontology)
    Download
    Models ( 0 )
    Allele
    Disease
    Evidence
    References
    Interactions ( 0 )
    Allele
    Disease
    Interaction
    References
    Comments ( 0 )
     
    Human Orthologs (via DIOPT v7.1)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Homo sapiens (Human)
    Gene name
    Score
    OMIM
    OMIM Phenotype
    Complementation?
    Transgene?
    Functional Complementation Data
    Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
    Interactions
    Summary of Physical Interactions
    esyN Network Diagram
    Show neighbor-neighbor interactions:
    Select Layout:
    Legend:
    Protein
    RNA
    Selected Interactor(s)
    Interactions Browser

    Please look at the Interaction Group reports for full details of the physical interactions
    protein-protein
    Interacting group
    Assay
    References
    Summary of Genetic Interactions
    esyN Network Diagram
    esyN Network Key:
    Suppression
    Enhancement

    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Subunit Structure (UniProtKB)
    Homodimer (By similarity). Interacts with mod(mdg4) (PubMed:21304601). Interacts with barr (PubMed:8978614, PubMed:11172718). Interacts with ph-p (PubMed:11172718). Interacts with mle; the interaction mediates association with the MSL dosage compensation complex (PubMed:23989663).
    (UniProt, P15348 )
    Linkouts
    InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
    Pathways
    Gene Group - Pathway Membership (FlyBase)
    External Data
    Linkouts
    Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    2L
    Recombination map
    2-54
    Cytogenetic map
    Sequence location
    2L:19,447,365..19,453,490 [-]
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    37E1-37E1
    Limits computationally determined from genome sequence between P{EP}dntEP2158 and P{EP}EP623&P{PZ}spi01068
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    37D2-37D6
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Location
    Left of (cM)
    Right of (cM)
    Notes
    Maps very close to RanGap.
    Stocks and Reagents
    Stocks (11)
    Genomic Clones (19)
    cDNA Clones (138)
     

    Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequences
    BDGP DGC clones
    Other clones
      Drosophila Genomics Resource Center cDNA clones

      For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

        cDNA Clones, End Sequenced (ESTs)
        RNAi and Array Information
        Linkouts
        Antibody Information
        Laboratory Generated Antibodies
         
        Commercially Available Antibodies
         
        Other Information
        Relationship to Other Genes
        Source for database identify of
        Source for database merge of
        Source for merge of: Top2 suo
        Additional comments
        Other Comments
        Reduction of Top2 via RNAi affects gypsy-induced phenotypes.
        RNAi screen using dsRNA made from templates generated with primers directed against this gene results in defects in chromosome condensation and chromosome misalignment on the metaphase spindle when assayed in S2 cells. This phenotype can be observed when the screen is performed with or without Cdc27 dsRNA.
        Expression is enriched in embryonic gonads.
        Mutant males are sterile, showing disruption of chromosome segregation during both meiotic divisions. The chromosomes segregate to one pole only in more than half of telophases I, resulting in many secondary spermatocytes that completely lack chromosomes. Bipolar spindles are formed in these spermatocytes and the spindles undergo the same dynamic transformations as seen in normal meiotic divisions.
        Area matching Drosophila Type II topoisomerase gene, Acc. No. X61209.
        Amino acid residue Lys 359 is critical for the catalytic activity of Top2.
        In a sample of 79 genes with multiple introns, 33 showed significant heterogeneity in G+C content among introns of the same gene and significant positive correspondence between the intron and the third codon position G+C content within genes. These results are consistent with selection adding against preferred codons at the start of genes.
        The functional interaction domain for quinolones is mapped and the site of action is shown to overlap with the domain for etoposide, amsacrine and genistein. Results support the hypothesis that many DNA cleavage-enhancing drugs share a common interaction domain on the enzyme.
        Several forms of spontaneous DNA damage are capable of acting as endogenous poisons of Top2.
        Apurinic sites located within the base of the 5' overhang generated by Top2-mediated DNA scission cause levels of enzyme-associated DNA breaks to increase. Conversely apurinic sites located immediately outside the cleavage overhang inhibits DNA scission. Results indicate apurinic sites have a profound influence on the activity of Top2 enzyme and act as position-specific Top2 positions.
        A chromatin-accessibility complex (CHRAC), which uses energy to increase the general accessibility of DNA in chromatin, has been identified. CHRAC can also function during chromatin assembly, using ATP to convert irregular chromatin into a regular array of nucleosomes with even spacing. CHRAC contains 5 subunits, two of which have been identified as the Iswi and Top2 gene products.
        barr protein associates with Top2 protein and affects its activity, this suggests barr protein functions in chromatid decatenation during the metaphase-anaphase transition.
        Etoposide.Top2 interactions (rather than etoposide.DNA interactions) mediate enzyme-DNA cleavage complex formation. Maximal levels of etoposide-induced scission reflect the ability of the drug to inhibit religation at specific sequences rather than affinity of the drug to site-specific enzyme.DNA complexes.
        Staurosporine inhibits catalytic activity of Top2 by blocking the transfer of phosphodiester bonds from DNA to the active tyrosine site. Other inhibitors most likely inactivate Top2 by alkylation of essential amino acids.
        Abasic sites are potent enhancers of double strand DNA cleavage mediated by Top2. Results suggest abasic sites represent cellular Top2 poisons and implies anticancer drugs mimic actions of these endogenous DNA lesions.
        Top2 is involved in protein-protein interactions that maintain nuclear localisation of Top2. Top2 has both RNA- and DNA-dependent anchorages in embryo nuclei.
        Topoisomerase 2 is distributed throughout interphase nuclei, except for the nucleoli, as judged by antibody staining. In some areas of nuclei localisation is not coincident with chromatin.
        The ability of Top2 to cleave an oligonucleotide containing a hairpin has been studied.
        Genetic and biochemical properties of a series of insertion linker mutations is used to analyse the domain structure of Top2.
        Most Top2 in cell free extracts of 0-2hr embryos appears to be nonnuclear and soluble. This pool of Top2 is detectable in situ and can be detected in extracts from older (16-19hr) embryos and Kc tissue cells. These nonnuclear Top2 containing particles are composed largely of Top2 and an unknown RNA molecule(s).
        Top2 is a Z-DNA binding protein, DNA binding characteristics are determined by filter binding and gel retardation. The Z-DNA binding activity of undegraded Top2 may be important in targetting the enzyme both to structural motifs required for chromatin organisation and to sites of local supercoiling.
        Anti-Top2 antibodies or epipodophylotoxin VM26 injected into blastoderm embryos inhibits Top2 activity and prevents or hinders anaphase segregation of chromatids. High concentrations of inhibitors block chromosome condensation and the arrangement of chromosomes on the metaphase plate.
        The effect of Pkc53E mediated phosphorylation on each step of Top2 catalytic cycle is analysed. As with Casein kinase II (CkIIβ and CkIIβ), stimulation of enzyme activity by Pkc53E correlates with an increased rate of Top2 catalysed ATP hydrolysis. Modification did not affect any step of the enzymes catalytic cycle that preceded the ATPase step.
        The effects of several drugs on the DNA strand passage event mediated by Top2 have been analysed.
        Top2-mediated DNA cleavage in the 5' region of an Hsp70 gene has been analysed.
        Top2 is involved in different functions of the 1731 LTR.
        In defining the relationships between drug classes and their interaction domains on Top2 results indicate that there are mechanistic differences between etoposide and a number of other Top2-targeted antineoplastic agents and that the interaction domain of novobocin on the enzyme does not overlap those of several DNA cleavage-enhancing drugs.
        The distribution of microinjected fluorescently labelled Top2 has been monitored using time-lapse, three dimensional movies. Experiments show Top2 is localised to the nucleus and on chromosomes is spatially and temporally regulated.
        To investigate the potential role for the passage helix in enzyme-mediated DNA cleavage, interactions between Top2 and a 40bp oligonucleotide that contains a specific enzyme recognition/cleavage sequence are characterised. Results indicate that the enzyme has to interact with more than a single double-stranded 40-mer in order for nucleic acid breakage to take place.
        The effects of casein kinase II-mediated phosphorylation on the individual steps of the enzymes catalytic cycle are characterised. Results strongly suggest that modification stimulates the activity of Top2 by enhancing the ability of the enzyme to hydrolyse its high energy ATP cofactor.
        Top2 can mediate illegitimate recombination events, at least in vitro, by a mechanism that does not rely on double-stranded DNA cleavage or subunit exchange.
        The interaction of Top1 and Top2 gene products with transcriptionally active and inactive Act5C, Act57B and Hsp70B has been compared. Topoisomerase II binding to actin and Hsp70B sequences occurs on both transcriptionally active and inactive chromatin. An unusual type of topoisomerase II binding site was identified which is associated with the 5' ends of inactive Hsp70 and actin genes, suggesting that this enzyme may be associated with repression of gene transcription.
        Formation of DNA/Top2 complexes have been demonstrated using CsCl equilibrium density centrifugation: three types of complex that are in equilibrium with each other exist. The complex formed in the presence of the VM26 tumour suppressor is extremely stable.
        8-methoxycaffeine has been demonstrated to inhibit the activity of Top2 by interfering with the interaction of Top2 with DNA.
        Effects of short-wave UV-induced photoproducts on the enzymatic activity of Top2 are investigated. DNA relaxation reaction is inhibited and this correlates with an inhibition of the enzyme DNA strand passage event. Results suggest repair of cyclobutane pyrimidine dimers is important for the catalytic function of Top2.
        Top2 enzyme activity has been studied.
        EM is used to further characterise the Top2-DNA complex and to directly visualize the position of Top2 molecules on DNA containing sequence-directed bends.
        The Top2 gene lies immediately adjacent to the location of the tandem duplication shown to be specific to RanGapSD chromosomes, and falls within the region from which several RanGapSD-related transcripts are encoded. However no obvious difference in Top2 transcription could be detected in RanGapSD mutant flies.
        Pre- and post-strand passage DNA cleavage complexes of Top2 serve as physiological targets for structurally disparate antineoplastic drugs.
        The effects of CP-67,804 and CP-115,953, two novel quinolone derivatives, on the enzymatic activity of Top2 are characterised. Both drugs enhance the pre- and poststrand passage DNA strand cleavage, neither inhibited the ability to religate cleaved DNA. Results strongly suggest CP-67,804 and CP-115,953 represent a novel class of Top2-targeted drugs.
        Top2 mediated cleavage of single-stranded DNA takes pace prior to the addition of SDS in an in vitro system.
        Structurally disparate class of Top2 targeted antineoplastic drugs stabilise the enzyme's DNA cleavage complex primarily by interfering with the ability of Top2 to religate DNA.
        Top2 enzyme recognises supercoiled DNA at least in part by interacting preferentially with crossover points on DNA.
        A number of anon-topo sites have been mapped and sequenced to study the sequence specificity of double strand DNA cleavage by Top2.
        DNA molecules with topological knots are detected in a reaction mixture containing circular DNA and purified Top2 enzyme. This knotting reaction has been characterised.
        Top2 protein has been purified and characterised.
        The relaxation of negatively supercoiled circular DNA by purified Top2 enzyme has been studied.
        The cleavage of double strand DNA by Top2 enzyme has been studied.
        Top2 is an essential gene that encodes the large subunit of type II DNA topoisomerase, an enzyme believed to play an important role in the condensation, decondensation, and segregation of chromosomes. The enzyme is a major component of the nuclear matrix of Drosophila cells (Berrios, Osheroff and Fisher, 1985) and is distributed along polytene chromosomes paralleling the distribution of the DNA (Heller, Shelton, Dietrich, Elgin and Brutlag, 1986). It is believed to act by passing a DNA segment through a transient double-stranded break in another segment. Major cleavage sites for type II topoisomerase have been found in nontranscribed spacer segments and in the 5' and 3' ends of Hsp70 and the histone genes (Udvardy, Schedl, Sander and Hsieh, 1985). When prepared from embryos, the purified enzyme is made up of a major polypeptide encoded by Top2 of 166,000 daltons, with binding sites for both DNA and ATP, and, in addition, smaller polypeptides of 30,000-40,000 and 132,000-145,000 daltons (Sander and Hsieh, 1983; Shelton, Osheroff and Brutlag, 1983; Heller, Shelton, Dietrich, Elgin and Brutlag, 1986). Protein kinase activity is associated with Drosophila topoisomerase II (Sander, Nolan and Hsieh, 1984; Ackerman, Glover and Osheroff, 1985).
        Origin and Etymology
        Discoverer
        Etymology
        Identification
        External Crossreferences and Linkouts ( 53 )
        Crossreferences
        NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
        GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
        RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
        UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
        Linkouts
        Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
        FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
        InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
        KEGG Genes - Molecular building blocks of life in the genomic space.
        Synonyms and Secondary IDs (29)
        Reported As
        Symbol Synonym
        Name Synonyms
        DNA Topoisomerase II
        DNA Topoisomeriase II
        Topoisomerase2
        topoisomerase 2
        type II DNA topoisomerase
        type II topoisomerase
        Secondary FlyBase IDs
        • FBgn0003732
        • FBgn0061478
        Datasets (1)
        Study focus (1)
        Experimental Role
        Project
        Project Type
        Title
        • bait_protein
        Genome-wide localization of chromosomal proteins in cell lines by ChIP-chip and ChIP-Seq.
        References (277)