The Fml1-MHF complex suppresses inter-fork strand annealing in fission yeast

  1. Io Nam Wong
  2. Jacqueline P S Neo
  3. Judith Oehler
  4. Sophie Schafhauser
  5. Fekret Osman
  6. Stephen B Carr
  7. Matthew C Whitby  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. Research Complex at Harwell, Rutherford Appleton Laboratory, United Kingdom

Abstract

Previously we reported that a process called inter-fork strand annealing (IFSA) causes genomic deletions during the termination of DNA replication when an active replication fork converges on a collapsed fork (Morrow et al., 2017). We also identified the FANCM-related DNA helicase Fml1 as a potential suppressor of IFSA. Here, we confirm that Fml1 does indeed suppress IFSA, and show that this function depends on its catalytic activity and ability to interact with Mhf1-Mhf2 via its C-terminal domain. Finally, a plausible mechanism of IFSA suppression is demonstrated by the finding that Fml1 can catalyse regressed fork restoration in vitro.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Author details

  1. Io Nam Wong

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4500-1758
  2. Jacqueline P S Neo

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Judith Oehler

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8397-6492
  4. Sophie Schafhauser

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Fekret Osman

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Stephen B Carr

    Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Matthew C Whitby

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    For correspondence
    matthew.whitby@bioch.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0951-3374

Funding

Biotechnology and Biological Sciences Research Council (BB/P019706/1)

  • Matthew C Whitby

Wellcome (090767/Z/09/Z)

  • Matthew C Whitby

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2019, Wong et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Io Nam Wong
  2. Jacqueline P S Neo
  3. Judith Oehler
  4. Sophie Schafhauser
  5. Fekret Osman
  6. Stephen B Carr
  7. Matthew C Whitby
(2019)
The Fml1-MHF complex suppresses inter-fork strand annealing in fission yeast
eLife 8:e49784.
https://doi.org/10.7554/eLife.49784

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https://doi.org/10.7554/eLife.49784