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Online Reference Material

ONLINE SEQUENCE DATABASES
Topoisomerase sequences are available from several online sources. However there are significant differences in how well defined the results are and in how succintly the information is displayed. Some display every little fragment ever reported plus extraneous unrelated ones too, while others just show complete sequences. There are variations in availability of boolean operators to narrow or widen searches. Some hyperlink further on to medline reference text and motif servers. Some require more steps of linking (and waiting for server response) than others to get the desired information. It is unfortunate that at the present time many of the servers are not able to distinguish in the search between topo I and II and separating them is an annoying and slow manual chore.

With each server below is the (number of sequences reported). For comparison, NEntrez found 152 sequences, of which 1/3 were short fragments. GCG stringsearch located 88 PIR and 78 Swissprot.

Topoisomerase Protein Sequence Searches:

  • GDB Enzyme Swissprot: topo I (15 seq). topo II (42 seq). Provides accession number & species code name. Links to sequence and can link further to Prosite, Prodom, Genbank, etc.
  • Entrez Browser (nih) SwissProt + PIR (200 limit) text= topoisomerase (200 seq of 216); or EC#= 5.99.1.* (~100 seq) . select top2 (25 entries). Provides species code name, 200 limit. Links to sequence report, fasta format, medline, neighbors, genbank.
  • srs (finland) SwissProt + PIR topoisomerase (159 seq) topoisomerase and II (47 seq)
  • srs (IU) SwissProt topoisomerase (70)
  • PIR:
    via nih (on topoisomerase+II) (27 seq-only topo II) via nih (on topoisomerase+I) (~75 seq-topo I&II) Provides pir#, name, EC#, species. Links to sequence.
    via gdb (on topoisomerase) (65 seq) or via gdb (on topoisomerase and II) (12 seq) Provides pir#, name, species . Links to sequence and further to Genbank + DDBJ + EC + Refbase.
    via gdb, title= topoisomerase (79 seq - topo I&II); can't save results location but link to analysis compensates. Provides pir#, name, species; can't keep result location. Links to sequence and further to blast/fasta.
    via UI on topoisomerase (91 seq - topo I&II) Provides pir#, name, EC#, species; can't keep result. Links to sequence.
    via gopher (~84 seq - topo I&II). Provides pir#, name, EC#, species. Links to sequence.
    bchs UHouston? (15)
  • Swiss-Prot: via Prodom (63) showing label, ac#, #bp, name via NIH (78)
    expasy DE/ID (40) or expasy on topoisomerase (162 seq - topo I&II & some related replication prot) Provides code name, EC#, species. Link to seq & on to prosite, medline, prodom, etc.
    IU on topoisomerase (88 seq I&II, some extraneous) Provides ac#, name, EC#. Link to seq.
  • OWL SwissProt + PIR nonredundant) (95 seq - topo I&II mixed up with some nontopo sequences); Provides enzyme nonunique name. Links to header and further to sequence, PIR, EMBL, Genbank, Prosite, etc

    Sequence Analysis:

  • Blocks search
  • Prosite: topo II via finland srsc with links to seq or via gdb/nih gopher ; or topo I Euk via finland srsc ; or topo I Prok via finland srsc
  • Prodom: on 'topoisomerase' via sanger ~60 matches graphic align of 36 sw seq, via tolouse
  • SCOP leucine zipper links to pdb structure

  • Comprehensive Sequence Searches:
    Genebank (141) + SwissProt (77) + PIR (83) NIH
    Genebank (141) + SwissProt (77) + PIR (39) via harvard
    Genebank (167) + SwissProt (70) + PIR (85) + EMBL (204), Trembl ( 94) via embl-srsc
    Genebank (171) + SwissProt (66) + PIR (84) + EMBL (185), Trembl (114) via embnet-srsc
    Genebank (---) + SwissProt (95) + PIR (86) + EMBL (202) via ebi-srsc
    Genebank (---) + SwissProt (95) + PIR (84) + EMBL (158) via finland-srsc

  • Gene Sequence Searches:
    Genbank via embl srsc (167) Genbank via UInd (~150) plus a few updates
  • EMBL via embnet, slow (~80)
  • EMBL via finland srsc (155)
  • DNA db of Japan search (~90)
  • Transcription Factor Entry at NIH (2)
    Go back up to Contents ^
    Online Medline Abstracts

    You may click on the following links for quick access to informative abstracts about topoisomerase (search term in quotes) provided by NIH PubMedline (ncbi genetics subset):

    ~5400 "topoisomerase"
    on 'topoisomerase+human' (~600 references)
    on 'topoisomerase+structure (~280 references)
    You can search by keyword through some of the SRS servers
    under their box: 'Search bibliographic libraries'

    other web topo pages


    Go back up to Contents ^


    References
    -
    -Champoux JJ (1981) "DNA is Linked to the Nicking Closing Enzyme by a Phosphodiesterase Bond to Tyrosine" J Biol Chem 256(10) 4805-9. -
    -Champoux JJ (1990) "Topoisomerase I Mechanism" in "DNA Topology and its Biological Effects" Cozzarelli NR & Wang JC (eds) Cold Spring Harbor Pr]. -
    -Kunze N (1989) et al "Localization of the active type I DNA topoisomerase gene on human chromosome 20q11.2-13.1" Hum Genet 84: 6-10 -
    Net search engines on 'topoisomerase': altavista - lycos -
    webmedlit recent references -

    Evolution of Topo

    The literature generally says that eukaryotic top i & ii relaxes both neg & pos supercoils whereas prokaryotic enzymes relax only neg supercoils BUT it is hard to know how much of this is an artifact of the limited methods of analysis.
    When topo transiently breaks dna backbone it simultaneously forms proten dna link in which a tyr O in enz is joined to a dna P at one end of the enzyme severed dna strand
    mitochondrial DNA of trypanosomes is linearized when the cells are treated with topo II inhibitors (epipodophyllotoxins, ellipticine, etc) but not by topo I inhibitors (novobiocin & quinolones). A maximum of 12% of all minicircles is cleaved in the presence of VP16-213, indicating there are at least 600 molecules of mitochondrial type II topoisomerase/cell or about one enzyme/8 kilobases of minicircle DNA. J Biol Chem 264: 4173-8 (1989) Shapiro TA; Klein VA; Englund PT
    Mitochondria, assayed for their ability to maintain a transmembrane potential (rhodamine 123 retention), as well as the lysosomal proton pump (probed by supravital uptake of acridine orange) remain unchanged in camptothecin treated cells. Exp Cell Res 193: 27-35 (1991) Del Bino G; Lassota P; Darzynkiewicz Z [was probing long enough to reflect transcription change of camp. in mitochondria-?sb]
    Type I topoisomerases have been purified from nuclei and mitochondria of human acute lymphoblastic leukemia cells Proc Natl Acad Sci U S A 83: 1680-4 (1986) Castora FJ; Kelly WG [nuclear contamination of mitochondria possible; lymphoblasts abnormal]
    If mitochondria are of phage origin why would there be some reports of it containing the more modern type II topo?
    What is the difference in roles of I and II topo? If topo I works why would a second, more complex one develop.

    Topo may be part of replication complex Malkas & Hickey (UMd)

    The gene organization has been determined for an 8-kb portion of the Streptomyces coelicolor chromosome close to the origin of DNA replication (oriC). revealed the presence of five open reading frames (ORFs) oriented in the same direction The deduced products of three of the ORFs have been identified as the S. coelicolor homologs of RecF, GyrB and GyrA. The recF gene is flanked by two ORFs, one of which encodes a protein with significant similarity to 6-phosphogluconate dehydrogenases (6PGDH) Gene organization in the dnaA-gyrA region of the Streptomyces coelicolor chromosome. Calcutt MJ Department of Biochemistry, University of Missouri-Columbia 65212. Gene 151: 23-8 (1994) medline


    1995 Soaring Bear bear@ellington.pharm.arizona.edu.