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BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment

Author

Listed:
  • Giuseppina D’Alessandro

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Donna Rose Whelan

    (NYU School of Medicine)

  • Sean Michael Howard

    (Università della Svizzera italiana)

  • Valerio Vitelli

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Xavier Renaudin

    (University of Cambridge)

  • Marek Adamowicz

    (IFOM, the FIRC Institute of Molecular Oncology
    University of Sussex, Falmer)

  • Fabio Iannelli

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Corey Winston Jones-Weinert

    (IFOM, the FIRC Institute of Molecular Oncology)

  • MiYoung Lee

    (University of Cambridge)

  • Valentina Matti

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Wei Ting C. Lee

    (NYU School of Medicine)

  • Michael John Morten

    (NYU School of Medicine)

  • Ashok Raraakrishnan Venkitaraman

    (University of Cambridge)

  • Petr Cejka

    (Università della Svizzera italiana
    Swiss Federal Institute of Technology)

  • Eli Rothenberg

    (NYU School of Medicine)

  • Fabrizio d’Adda di Fagagna

    (IFOM, the FIRC Institute of Molecular Oncology
    Consiglio Nazionale delle Ricerche (IGM-CNR))

Abstract

DNA double-strand breaks (DSBs) are toxic DNA lesions, which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-phase cells, dilncRNAs pair to the resected DNA ends and form DNA:RNA hybrids, which are recognized by BRCA1. We also show that BRCA2 directly interacts with RNase H2, mediates its localization to DSBs in the S/G2 cell-cycle phase, and controls DNA:RNA hybrid levels at DSBs. These results demonstrate that regulated DNA:RNA hybrid levels at DSBs contribute to HR-mediated repair.

Suggested Citation

  • Giuseppina D’Alessandro & Donna Rose Whelan & Sean Michael Howard & Valerio Vitelli & Xavier Renaudin & Marek Adamowicz & Fabio Iannelli & Corey Winston Jones-Weinert & MiYoung Lee & Valentina Matti &, 2018. "BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07799-2
    DOI: 10.1038/s41467-018-07799-2
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