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Bloom helicase mediates formation of large single–stranded DNA loops during DNA end processing

Author

Listed:
  • Chaoyou Xue

    (Columbia University
    Chinese Academy of Sciences)

  • Sameer J. Salunkhe

    (University of Texas Health Science Center at San Antonio
    University of Texas Health Science Center at San Antonio)

  • Nozomi Tomimatsu

    (Chinese Academy of Sciences)

  • Ajinkya S. Kawale

    (University of Texas Health Science Center at San Antonio
    Harvard Medical School)

  • Youngho Kwon

    (University of Texas Health Science Center at San Antonio
    University of Texas Health Science Center at San Antonio)

  • Sandeep Burma

    (University of Texas Health Science Center at San Antonio
    University of Texas Health Science Center at San Antonio)

  • Patrick Sung

    (University of Texas Health Science Center at San Antonio
    University of Texas Health Science Center at San Antonio)

  • Eric C. Greene

    (Columbia University)

Abstract

Bloom syndrome (BS) is associated with a profoundly increased cancer risk and is caused by mutations in the Bloom helicase (BLM). BLM is involved in the nucleolytic processing of the ends of DNA double–strand breaks (DSBs), to yield long 3′ ssDNA tails that serve as the substrate for break repair by homologous recombination (HR). Here, we use single–molecule imaging to demonstrate that BLM mediates formation of large ssDNA loops during DNA end processing. A BLM mutant lacking the N–terminal domain (NTD) retains vigorous in vitro end processing activity but fails to generate ssDNA loops. This same mutant supports DSB end processing in cells, however, these cells do not form RAD51 DNA repair foci and the processed DSBs are channeled into synthesis–dependent strand annealing (SSA) instead of HR–mediated repair, consistent with a defect in RAD51 filament formation. Together, our results provide insights into BLM functions during homologous recombination.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29937-7
    DOI: 10.1038/s41467-022-29937-7
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    1. Zita Gál & Stavroula Boukoura & Kezia Catharina Oxe & Sara Badawi & Blanca Nieto & Lea Milling Korsholm & Sille Blangstrup Geisler & Ekaterina Dulina & Anna Vestergaard Rasmussen & Christina Dahl & We, 2024. "Hyper-recombination in ribosomal DNA is driven by long-range resection-independent RAD51 accumulation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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