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PMID: 12433984 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The Bloom's syndrome helicase stimulates the activity of human topoisomerase IIIalpha.

Nucleic acids research ·Vol. 30 ·No. 22 ·2002-11-15 ·Pages 4823-9

Wu L, Hickson ID

Abstract

Bloom's syndrome (BS) is a disorder associated with chromosomal instability and a predisposition to the development of cancer. The BS gene product, BLM, is a DNA helicase of the RecQ family that forms a complex in vitro and in vivo with topoisomerase IIIalpha. Here, we show that BLM stimulates the ability of topoisomerase IIIalpha to relax negatively supercoiled DNA. Moreover, DNA binding analyses indicate that BLM recruits topoisomerase IIIalpha to its DNA substrate. Consistent with this, a mutant form of BLM that retains helicase activity, but is unable to bind topoisomerase IIIalpha, fails to stimulate topoisomerase activity. These results indicate that a physical association between BLM and topoisomerase IIIalpha is a prerequisite for their functional biochemical interaction.

MeSH Terms
Adenosine Triphosphatases/genetics,metabolism,pharmacology DNA Helicases/genetics,metabolism,pharmacology DNA Topoisomerases, Type I/metabolism DNA, Single-Stranded/chemistry,metabolism DNA, Superhelical/metabolism Enzyme Activation Humans Mutation Nucleic Acid Conformation Protein Transport RecQ Helicases
Chemicals
DNA, Single-Stranded DNA, Superhelical Adenosine Triphosphatases Bloom syndrome protein DNA Helicases RecQ Helicases DNA Topoisomerases, Type I
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Wu Leonard
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Hickson Ian D
References (46)
46 references, click to expand
  1. Generation of double-stranded breaks in hypernegatively supercoiled DNA by Drosophila topoisomerase IIIbeta, a type IA enzyme.
    J Biol Chem. 2002 Jul 26;277(30):26865-71 PMID: 12023976
  2. DNA topoisomerases: structure, function, and mechanism.
    Annu Rev Biochem. 2001;70:369-413 PMID: 11395412
  3. A manyfold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes.
    Proc Natl Acad Sci U S A. 1974 Nov;71(11):4508-12 PMID: 4140506
  4. Isolation and genetic characterization of a thymineless death-resistant mutant of Escherichia coli K12: identification of a new mutation (recQ1) that blocks the RecF recombination pathway.
    Mol Gen Genet. 1984;195(3):474-80 PMID: 6381965
  5. A hyper-recombination mutation in S. cerevisiae identifies a novel eukaryotic topoisomerase.
    Cell. 1989 Jul 28;58(2):409-19 PMID: 2546682
  6. Mutator phenotype of Werner syndrome is characterized by extensive deletions.
    Proc Natl Acad Sci U S A. 1989 Aug;86(15):5893-7 PMID: 2762303
  7. Bloom syndrome: a mendelian prototype of somatic mutational disease.
    Medicine (Baltimore). 1993 Nov;72(6):393-406 PMID: 8231788
  8. The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase.
    Mol Cell Biol. 1994 Dec;14(12):8391-8 PMID: 7969174
  9. The Bloom's syndrome gene product is homologous to RecQ helicases.
    Cell. 1995 Nov 17;83(4):655-66 PMID: 7585968
  10. Positional cloning of the Werner's syndrome gene.
    Science. 1996 Apr 12;272(5259):258-62 PMID: 8602509
  11. Human TOP3: a single-copy gene encoding DNA topoisomerase III.
    Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3653-7 PMID: 8622991
  12. DNA topoisomerases.
    Annu Rev Biochem. 1996;65:635-92 PMID: 8811192
  13. SGS1, a homologue of the Bloom's and Werner's syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae.
    Genetics. 1996 Nov;144(3):935-45 PMID: 8913739
  14. RecQ DNA helicase is a suppressor of illegitimate recombination in Escherichia coli.
    Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3860-5 PMID: 9108069
  15. rqh1+, a fission yeast gene related to the Bloom's and Werner's syndrome genes, is required for reversible S phase arrest.
    EMBO J. 1997 May 15;16(10):2682-92 PMID: 9184215
  16. The Bloom's syndrome gene product is a 3'-5' DNA helicase.
    J Biol Chem. 1997 Dec 5;272(49):30611-4 PMID: 9388193
  17. Mammalian DNA topoisomerase IIIalpha is essential in early embryogenesis.
    Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1010-3 PMID: 9448276
  18. RecQ helicase, in concert with RecA and SSB proteins, initiates and disrupts DNA recombination.
    Genes Dev. 1998 Apr 15;12(8):1134-44 PMID: 9553043
  19. The Bloom's syndrome helicase unwinds G4 DNA.
    J Biol Chem. 1998 Oct 16;273(42):27587-92 PMID: 9765292
  20. Cloning of cDNA encoding a novel mouse DNA topoisomerase III (Topo IIIbeta) possessing negatively supercoiled DNA relaxing activity, whose message is highly expressed in the testis.
    J Biol Chem. 1998 Oct 30;273(44):28553-6 PMID: 9786843
  21. The essential role of yeast topoisomerase III in meiosis depends on recombination.
    EMBO J. 1999 Mar 15;18(6):1701-11 PMID: 10075939
  22. Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome.
    Nat Genet. 1999 May;22(1):82-4 PMID: 10319867
  23. RecQ helicase and topoisomerase III comprise a novel DNA strand passage function: a conserved mechanism for control of DNA recombination.
    Mol Cell. 1999 May;3(5):611-20 PMID: 10360177
  24. Purification and characterization of human DNA topoisomerase IIIalpha.
    Nucleic Acids Res. 1999 Jun 15;27(12):2443-50 PMID: 10352172
  25. Binding specificity determines polarity of DNA unwinding by the Sgs1 protein of S. cerevisiae.
    J Mol Biol. 1999 Jun 4;289(2):235-48 PMID: 10366502
  26. Topoisomerase III is essential for accurate nuclear division in Schizosaccharomyces pombe.
    Nucleic Acids Res. 1999 Oct 15;27(20):4050-8 PMID: 10497270
  27. PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1.
    J Cell Biol. 1999 Oct 18;147(2):221-34 PMID: 10525530
  28. The top3(+) gene is essential in Schizosaccharomyces pombe and the lethality associated with its loss is caused by Rad12 helicase activity.
    Nucleic Acids Res. 1999 Dec 15;27(24):4715-24 PMID: 10572171
  29. Cloning and characterization of Drosophila topoisomerase IIIbeta. Relaxation of hypernegatively supercoiled DNA.
    J Biol Chem. 2000 Jan 21;275(3):1533-40 PMID: 10636841
  30. A role for PML and the nuclear body in genomic stability.
    Oncogene. 1999 Dec 23;18(56):7941-7 PMID: 10637504
  31. RecQ family helicases: roles in cancer and aging.
    Curr Opin Genet Dev. 2000 Feb;10(1):32-8 PMID: 10679384
  32. Association of the Bloom syndrome protein with topoisomerase IIIalpha in somatic and meiotic cells.
    Cancer Res. 2000 Mar 1;60(5):1162-7 PMID: 10728666
  33. The Bloom's syndrome gene product interacts with topoisomerase III.
    J Biol Chem. 2000 Mar 31;275(13):9636-44 PMID: 10734115
  34. The Bloom's syndrome gene product promotes branch migration of holliday junctions.
    Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6504-8 PMID: 10823897
  35. Binding and melting of D-loops by the Bloom syndrome helicase.
    Biochemistry. 2000 Nov 28;39(47):14617-25 PMID: 11087418
  36. BLM, the Bloom's syndrome protein, varies during the cell cycle in its amount, distribution, and co-localization with other nuclear proteins.
    Cytogenet Cell Genet. 2000;91(1-4):217-23 PMID: 11173860
  37. Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest.
    EMBO Rep. 2000 Jul;1(1):80-4 PMID: 11256630
  38. Mapping the DNA topoisomerase III binding domain of the Sgs1 DNA helicase.
    J Biol Chem. 2001 Mar 23;276(12):8848-55 PMID: 11124263
  39. DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders.
    Hum Mol Genet. 2001 Apr;10(7):741-6 PMID: 11257107
  40. Regulation and localization of the Bloom syndrome protein in response to DNA damage.
    J Cell Biol. 2001 Apr 16;153(2):367-80 PMID: 11309417
  41. Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability.
    Hum Mol Genet. 2001 Jun 1;10(12):1287-98 PMID: 11406610
  42. The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases.
    Nucleic Acids Res. 2001 Jul 1;29(13):2843-9 PMID: 11433031
  43. RecQ helicases and topoisomerases: components of a conserved complex for the regulation of genetic recombination.
    Cell Mol Life Sci. 2001 Jun;58(7):894-901 PMID: 11497238
  44. Association of yeast DNA topoisomerase III and Sgs1 DNA helicase: studies of fusion proteins.
    Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11108-13 PMID: 11553789
  45. Topoisomerase III acts upstream of Rad53p in the S-phase DNA damage checkpoint.
    Mol Cell Biol. 2001 Nov;21(21):7150-62 PMID: 11585898
  46. Roles of RecQ family helicases in the maintenance of genome stability.
    Cold Spring Harb Symp Quant Biol. 2000;65:573-81 PMID: 12760076
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkf611
Published
2002-11-15
Pages
4823-9
Language
English
Region
England
NLM ID
0411011
PMCID
PMC137159
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkf611 PMC Full Text View journal details
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