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Nat Commun. 2014 Jun 9;5:4091. doi: 10.1038/ncomms5091.

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

Author information

1
CRUK MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK.
2
Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, The University of Edinburgh, Swann Building, Mayfield Road, Edinburgh EH9 3JR, UK.
3
Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
4
University College London, Department of Genetics, Evolution and Environment, Darwin Building, Gower Street, London WC1E 6BT, UK.
#
Contributed equally

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.

PMID:
24909977
PMCID:
PMC4535359
DOI:
10.1038/ncomms5091
[Indexed for MEDLINE]
Free PMC Article

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