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PMID: 16024743 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

The Bloom's syndrome helicase promotes the annealing of complementary single-stranded DNA.

Nucleic acids research ·Vol. 33 ·No. 12 ·2005-00-00 ·Pages 3932-41

Cheok CF, Wu L, Garcia PL, Janscak P, Hickson ID

Abstract

The product of the gene mutated in Bloom's syndrome, BLM, is a 3'-5' DNA helicase belonging to the highly conserved RecQ family. In addition to a conventional DNA strand separation activity, BLM catalyzes both the disruption of non-B-form DNA, such as G-quadruplexes, and the branch migration of Holliday junctions. Here, we have characterized a new activity for BLM: the promotion of single-stranded DNA (ssDNA) annealing. This activity does not require Mg(2+), is inhibited by ssDNA binding proteins and ATP, and is dependent on DNA length. Through analysis of various truncation mutants of BLM, we show that the C-terminal domain is essential for strand annealing and identify a 60 amino acid stretch of this domain as being important for both ssDNA binding and strand annealing. We present a model in which the ssDNA annealing activity of BLM facilitates its role in the processing of DNA intermediates that arise during repair of damaged replication forks.

MeSH Terms
Adenosine Triphosphatases/chemistry,metabolism DNA Helicases/chemistry,metabolism DNA Repair DNA, Single-Stranded/chemistry,metabolism DNA-Binding Proteins/metabolism Models, Genetic Protein Structure, Tertiary RecQ Helicases
Chemicals
DNA, Single-Stranded DNA-Binding Proteins Adenosine Triphosphatases Bloom syndrome protein DNA Helicases RecQ Helicases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cheok Chit Fang
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital Oxford OX3 9DS, UK.
Wu Leonard
Garcia Patrick L
Janscak Pavel
Hickson Ian D
References (27)
27 references, click to expand
  1. Structure of the single-strand annealing domain of human RAD52 protein.
    Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13492-7 PMID: 12370410
  2. Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases.
    J Biol Chem. 2002 Oct 25;277(43):41110-9 PMID: 12181313
  3. Correlation of biochemical properties with the oligomeric state of human rad52 protein.
    J Biol Chem. 2002 Nov 29;277(48):46172-8 PMID: 12226092
  4. RecQ helicases: caretakers of the genome.
    Nat Rev Cancer. 2003 Mar;3(3):169-78 PMID: 12612652
  5. Characterization and mutational analysis of the RecQ core of the bloom syndrome protein.
    J Mol Biol. 2003 Jun 27;330(1):29-42 PMID: 12818200
  6. High-resolution structure of the E.coli RecQ helicase catalytic core.
    EMBO J. 2003 Oct 1;22(19):4910-21 PMID: 14517231
  7. Central role for the Werner syndrome protein/poly(ADP-ribose) polymerase 1 complex in the poly(ADP-ribosyl)ation pathway after DNA damage.
    Mol Cell Biol. 2003 Dec;23(23):8601-13 PMID: 14612404
  8. The Bloom's syndrome helicase suppresses crossing over during homologous recombination.
    Nature. 2003 Dec 18;426(6968):870-4 PMID: 14685245
  9. Werner syndrome protein contains three structure-specific DNA binding domains.
    J Biol Chem. 2003 Dec 26;278(52):52997-3006 PMID: 14534320
  10. Human RECQ5beta, a protein with DNA helicase and strand-annealing activities in a single polypeptide.
    EMBO J. 2004 Jul 21;23(14):2882-91 PMID: 15241474
  11. Bloom's syndrome.
    Dermatol Clin. 1995 Jan;13(1):7-18 PMID: 7712653
  12. The Bloom's syndrome gene product is a 3'-5' DNA helicase.
    J Biol Chem. 1997 Dec 5;272(49):30611-4 PMID: 9388193
  13. A putative nucleic acid-binding domain in Bloom's and Werner's syndrome helicases.
    Trends Biochem Sci. 1997 Nov;22(11):417-8 PMID: 9397680
  14. The Bloom's syndrome helicase unwinds G4 DNA.
    J Biol Chem. 1998 Oct 16;273(42):27587-92 PMID: 9765292
  15. Oligomeric ring structure of the Bloom's syndrome helicase.
    Curr Biol. 1999 Jun 3;9(11):597-600 PMID: 10359700
  16. RecQ family members combine strand pairing and unwinding activities to catalyze strand exchange.
    J Biol Chem. 2005 Jun 17;280(24):23397-407 PMID: 15845538
  17. The HRDC domain of BLM is required for the dissolution of double Holliday junctions.
    EMBO J. 2005 Jul 20;24(14):2679-87 PMID: 15990871
  18. The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins.
    Structure. 1999 Dec 15;7(12):1557-66 PMID: 10647186
  19. The Bloom's syndrome gene product interacts with topoisomerase III.
    J Biol Chem. 2000 Mar 31;275(13):9636-44 PMID: 10734115
  20. 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
  21. Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity.
    J Biol Chem. 2000 Aug 4;275(31):23500-8 PMID: 10825162
  22. Substrate-specific inhibition of RecQ helicase.
    Nucleic Acids Res. 2001 Apr 15;29(8):1765-71 PMID: 11292849
  23. 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
  24. Formation of Holliday junctions by regression of nascent DNA in intermediates containing stalled replication forks: RecG stimulates regression even when the DNA is negatively supercoiled.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8235-40 PMID: 11459958
  25. Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity.
    EMBO J. 2001 Oct 15;20(20):5791-801 PMID: 11598021
  26. Inhibition of the Bloom's and Werner's syndrome helicases by G-quadruplex interacting ligands.
    Biochemistry. 2001 Dec 18;40(50):15194-202 PMID: 11735402
  27. G4 DNA unwinding by BLM and Sgs1p: substrate specificity and substrate-specific inhibition.
    Nucleic Acids Res. 2002 Sep 15;30(18):3954-61 PMID: 12235379
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gki712
Published
2005-00-00
Epub
2005-00-15
Pages
3932-41
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1176015
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gki712 PMC Full Text View journal details
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