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

Leonard Wu, Kok Lung Chan, Christine Ralf, Douglas A. Bernstein, Patrick L. Garcia, Vilhelm A. Bohr, Alessandro Vindigni, Pavel Janscak, James L. Keck, Ian D. Hickson

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Abstract

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 IIIα (TOPO IIIα) 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.

Original languageEnglish
Pages (from-to)2679-2687
Number of pages9
JournalEMBO Journal
Volume24
Issue number14
DOIs
StatePublished - Jul 20 2005
Externally publishedYes

Keywords

  • Bloom's syndrome
  • HRDC domain
  • Holliday junction resolution
  • RecQ DNA helicases
  • Topoisomerase III

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    Wu, L., Chan, K. L., Ralf, C., Bernstein, D. A., Garcia, P. L., Bohr, V. A., Vindigni, A., Janscak, P., Keck, J. L., & Hickson, I. D. (2005). The HRDC domain of BLM is required for the dissolution of double Holliday junctions. EMBO Journal, 24(14), 2679-2687. https://doi.org/10.1038/sj.emboj.7600740