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Mechanistic insight into the interaction of BLM helicase with intra-strand G-quadruplex structures

Author

Listed:
  • Sujoy Chatterjee

    (New York University School of Medicine)

  • Jennifer Zagelbaum

    (New York University School of Medicine)

  • Pavel Savitsky

    (Genome Integrity group, Structural Genomics Consortium, University of Oxford)

  • Andreas Sturzenegger

    (Institute of Molecular Cancer Research, University of Zurich)

  • Diana Huttner

    (NovoNordisk Foundation Center for Protein Research, University of Copenhagen
    University of Copenhagen)

  • Pavel Janscak

    (Institute of Molecular Cancer Research, University of Zurich)

  • Ian D. Hickson

    (University of Copenhagen)

  • Opher Gileadi

    (Genome Integrity group, Structural Genomics Consortium, University of Oxford)

  • Eli Rothenberg

    (New York University School of Medicine)

Abstract

Bloom syndrome is an autosomal recessive disorder caused by mutations in the RecQ family helicase BLM that is associated with growth retardation and predisposition to cancer. BLM helicase has a high specificity for non-canonical G-quadruplex (G4) DNA structures, which are formed by G-rich DNA strands and play an important role in the maintenance of genomic integrity. Here we used single-molecule FRET to define the mechanism of interaction of BLM helicase with intra-stranded G4 structures. We show that the activity of BLM is substrate dependent, and highly regulated by a short-strand DNA (ssDNA) segment that separates the G4 motif from double-stranded DNA. We demonstrate cooperativity between the RQC and HRDC domains of BLM during binding and unfolding of the G4 structure, where the RQC domain interaction with G4 is stabilized by HRDC binding to ssDNA. We present a model that proposes a unique role for G4 structures in modulating the activity of DNA processing enzymes.

Suggested Citation

  • Sujoy Chatterjee & Jennifer Zagelbaum & Pavel Savitsky & Andreas Sturzenegger & Diana Huttner & Pavel Janscak & Ian D. Hickson & Opher Gileadi & Eli Rothenberg, 2014. "Mechanistic insight into the interaction of BLM helicase with intra-strand G-quadruplex structures," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6556
    DOI: 10.1038/ncomms6556
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    Cited by:

    1. Chaoyou Xue & Sameer J. Salunkhe & Nozomi Tomimatsu & Ajinkya S. Kawale & Youngho Kwon & Sandeep Burma & Patrick Sung & Eric C. Greene, 2022. "Bloom helicase mediates formation of large single–stranded DNA loops during DNA end processing," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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