IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5091.html
   My bibliography  Save this article

A histone H3K36 chromatin switch coordinates DNA double-strand break repair pathway choice

Author

Listed:
  • Chen-Chun Pai

    (CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford)

  • Rachel S. Deegan

    (CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford)

  • Lakxmi Subramanian

    (Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, The University of Edinburgh)

  • Csenge Gal

    (Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University)

  • Sovan Sarkar

    (CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford)

  • Elizabeth J. Blaikley

    (CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford)

  • Carol Walker

    (CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford)

  • Lydia Hulme

    (CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford)

  • Eric Bernhard

    (CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford)

  • Sandra Codlin

    (University College London, Evolution and Environment)

  • Jürg Bähler

    (University College London, Evolution and Environment)

  • Robin Allshire

    (Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, The University of Edinburgh)

  • Simon Whitehall

    (Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University)

  • Timothy C. Humphrey

    (CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford)

Abstract

DNA double-strand break (DSB) repair is a highly regulated process performed predominantly by non-homologous end joining (NHEJ) or homologous recombination (HR) pathways. How these pathways are coordinated in the context of chromatin is unclear. Here we uncover a role for histone H3K36 modification in regulating DSB repair pathway choice in fission yeast. We find Set2-dependent H3K36 methylation reduces chromatin accessibility, reduces resection and promotes NHEJ, while antagonistic Gcn5-dependent H3K36 acetylation increases chromatin accessibility, increases resection and promotes HR. Accordingly, loss of Set2 increases H3K36Ac, chromatin accessibility and resection, while Gcn5 loss results in the opposite phenotypes following DSB induction. Further, H3K36 modification is cell cycle regulated with Set2-dependent H3K36 methylation peaking in G1 when NHEJ occurs, while Gcn5-dependent H3K36 acetylation peaks in S/G2 when HR prevails. These findings support an H3K36 chromatin switch in regulating DSB repair pathway choice.

Suggested Citation

  • Chen-Chun Pai & Rachel S. Deegan & Lakxmi Subramanian & Csenge Gal & Sovan Sarkar & Elizabeth J. Blaikley & Carol Walker & Lydia Hulme & Eric Bernhard & Sandra Codlin & Jürg Bähler & Robin Allshire & , 2014. "A histone H3K36 chromatin switch coordinates DNA double-strand break repair pathway choice," Nature Communications, Nature, vol. 5(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5091
    DOI: 10.1038/ncomms5091
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5091
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5091?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5091. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.