FUS-dependent liquid–liquid phase separation is important for DNA repair initiation

DOI PDF 被引用文献3件
  • Brunno R. Levone
    Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy 1
  • Silvia C. Lenzken
    Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy 1
  • Marco Antonaci
    Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy 1
  • Andreas Maiser
    Department of Biology II, Center for Integrated Protein Science Munich, Ludwig Maximilian University of Munich, Planegg-Martinsried, Germany 2
  • Alexander Rapp
    Department of Biology, Technical University of Darmstadt, Darmstadt, Germany 3
  • Francesca Conte
    Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy 1
  • Stefan Reber
    UK Dementia Research Institute, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK 4
  • Jonas Mechtersheimer
    UK Dementia Research Institute, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK 4
  • Antonella E. Ronchi
    Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy 1
  • Oliver Mühlemann
    Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland 5
  • Heinrich Leonhardt
    Department of Biology II, Center for Integrated Protein Science Munich, Ludwig Maximilian University of Munich, Planegg-Martinsried, Germany 2
  • M. Cristina Cardoso
    Department of Biology, Technical University of Darmstadt, Darmstadt, Germany 3
  • Marc-David Ruepp
    UK Dementia Research Institute, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK 4
  • Silvia M.L. Barabino
    Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy 1

抄録

<jats:p>RNA-binding proteins (RBPs) are emerging as important effectors of the cellular DNA damage response (DDR). The RBP FUS is implicated in RNA metabolism and DNA repair, and it undergoes reversible liquid–liquid phase separation (LLPS) in vitro. Here, we demonstrate that FUS-dependent LLPS is necessary for the initiation of the DDR. Using laser microirradiation in FUS-knockout cells, we show that FUS is required for the recruitment to DNA damage sites of the DDR factors KU80, NBS1, and 53BP1 and of SFPQ, another RBP implicated in the DDR. The relocation of KU80, NBS1, and SFPQ is similarly impaired by LLPS inhibitors, or LLPS-deficient FUS variants. We also show that LLPS is necessary for efficient γH2AX foci formation. Finally, using superresolution structured illumination microscopy, we demonstrate that the absence of FUS impairs the proper arrangement of γH2AX nanofoci into higher-order clusters. These findings demonstrate the early requirement for FUS-dependent LLPS in the activation of the DDR and the proper assembly of DSB repair complexes.</jats:p>

収録刊行物

被引用文献 (3)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ