1. Chromosomes and Gene Expression

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
https://doi.org/10.7554/eLife.49784
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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.

Data availability

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

Article and author information

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.

Metrics

  • 1,317
    views
  • 214
    downloads
  • 4
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Citations by DOI

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

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

Categories and tags

Research organism

Further reading

    1. Chromosomes and Gene Expression

    Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replication

    Carl A Morrow, Michael O Nguyen ... Matthew C Whitby
    Research Article

    Problems that arise during DNA replication can drive genomic alterations that are instrumental in the development of cancers and many human genetic disorders. Replication fork barriers are a commonly encountered problem, which can cause fork collapse and act as hotspots for replication termination. Collapsed forks can be rescued by homologous recombination, which restarts replication. However, replication restart is relatively slow and, therefore, replication termination may frequently occur by an active fork converging on a collapsed fork. We find that this type of non-canonical fork convergence in fission yeast is prone to trigger deletions between repetitive DNA sequences via a mechanism we call Inter-Fork Strand Annealing (IFSA) that depends on the recombination proteins Rad52, Exo1 and Mus81, and is countered by the FANCM-related DNA helicase Fml1. Based on our findings, we propose that IFSA is a potential threat to genomic stability in eukaryotes.