Binding and melting of D-loops by the Bloom syndrome helicase

Biochemistry. 2000 Nov 28;39(47):14617-25. doi: 10.1021/bi0018640.


Bloom syndrome is a rare autosomal disorder characterized by predisposition to cancer and genomic instability. BLM, the structural gene mutated in individuals with the disorder, encodes a DNA helicase belonging to the RecQ family of helicases. These helicases have been established to serve roles in both promoting and preventing recombination. Mounting evidence has implicated a function for BLM during DNA replication; specifically, BLM might be involved in rescuing stalled or collapsed replication forks by a recombination-based mechanism. We have tested this idea by examining the binding and melting activity of BLM on oligonucleotide substrates containing D-loops, DNA structures that model the presumed initial intermediate formed during homologous recombination. We find that BLM preferentially melts those D-loops that are formed more favorably by the strand exchange protein Rad51, but whose polarity could be less favorable for enabling restoration of an active replication fork. We propose a model in which BLM selectively dissociates recombination intermediates likely to be unfavorable for recombination-promoted replication.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism*
  • Bloom Syndrome / enzymology*
  • Bloom Syndrome / genetics*
  • DNA Damage*
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Models, Genetic
  • Nucleic Acid Conformation*
  • Nucleic Acid Heteroduplexes / metabolism
  • Protein Binding
  • Rad51 Recombinase
  • RecQ Helicases
  • Recombination, Genetic
  • Substrate Specificity


  • DNA-Binding Proteins
  • Nucleic Acid Heteroduplexes
  • RAD51 protein, human
  • Rad51 Recombinase
  • Adenosine Triphosphatases
  • Bloom syndrome protein
  • DNA Helicases
  • RecQ Helicases