The HRDC domain of BLM is required for the dissolution of double Holliday junctions

EMBO J. 2005 Jul 20;24(14):2679-87. doi: 10.1038/sj.emboj.7600740. Epub 2005 Jun 30.


Bloom's syndrome is a hereditary cancer-predisposition disorder resulting from mutations in the BLM gene. In humans, BLM encodes one of five members of the RecQ helicase family. One function of BLM is to act in concert with topoisomerase IIIalpha (TOPO IIIalpha) to resolve recombination intermediates containing double Holliday junctions by a process called double Holliday junction dissolution, herein termed dissolution. Here, we show that dissolution is highly specific for BLM among human RecQ helicases and critically depends upon a functional HRDC domain in BLM. We show that the HRDC domain confers DNA structure specificity, and is required for the efficient binding to and unwinding of double Holliday junctions, but not for the unwinding of a simple partial duplex substrate. Furthermore, we show that lysine-1270 of BLM, which resides in the HRDC domain and is predicted to play a role in mediating interactions with DNA, is required for efficient dissolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Bloom Syndrome / genetics
  • Bloom Syndrome / metabolism
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • DNA, Cruciform / metabolism*
  • Humans
  • Lysine / metabolism
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • RecQ Helicases
  • Sequence Analysis, Protein


  • DNA, Cruciform
  • Adenosine Triphosphatases
  • Bloom syndrome protein
  • DNA Helicases
  • RecQ Helicases
  • Lysine