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Parallel genome-wide screens identify synthetic viable interactions between the BLM helicase complex and Fanconi anemia

Author

Listed:
  • Martin Moder

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Georgia Velimezi

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Michel Owusu

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Abdelghani Mazouzi

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Marc Wiedner

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Joana Ferreira da Silva

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Lydia Robinson-Garcia

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Fiorella Schischlik

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Rastislav Slavkovsky

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
    Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc)

  • Robert Kralovics

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Michael Schuster

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Christoph Bock

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Trey Ideker

    (Division of Genetics, University of California San Diego
    University of California San Diego
    Moores Cancer Center, University of California San Diego
    The Cancer Cell Map Initiative)

  • Stephen P. Jackson

    (The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Biochemistry, University of Cambridge
    The Wellcome Trust Sanger Institute)

  • Jörg Menche

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Joanna I. Loizou

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

Abstract

Maintenance of genome integrity via repair of DNA damage is a key biological process required to suppress diseases, including Fanconi anemia (FA). We generated loss-of-function human haploid cells for FA complementation group C (FANCC), a gene encoding a component of the FA core complex, and used genome-wide CRISPR libraries as well as insertional mutagenesis to identify synthetic viable (genetic suppressor) interactions for FA. Here we show that loss of the BLM helicase complex suppresses FANCC phenotypes and we confirm this interaction in cells deficient for FA complementation group I and D2 (FANCI and FANCD2) that function as part of the FA I-D2 complex, indicating that this interaction is not limited to the FA core complex, hence demonstrating that systematic genome-wide screening approaches can be used to reveal genetic viable interactions for DNA repair defects.

Suggested Citation

  • Martin Moder & Georgia Velimezi & Michel Owusu & Abdelghani Mazouzi & Marc Wiedner & Joana Ferreira da Silva & Lydia Robinson-Garcia & Fiorella Schischlik & Rastislav Slavkovsky & Robert Kralovics & M, 2017. "Parallel genome-wide screens identify synthetic viable interactions between the BLM helicase complex and Fanconi anemia," Nature Communications, Nature, vol. 8(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01439-x
    DOI: 10.1038/s41467-017-01439-x
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