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

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; Simon Whitehall; Timothy C. Humphrey

doi:10.1038/ncomms5091

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

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, Simon Whitehall, Timothy C. Humphrey^*

^*Corresponding author for this work

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Article number	4091
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5091
Publication status	Published - 9 Jun 2014

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@article{721a084add84479bb3d79bb1649492dd,

title = "A histone H3K36 chromatin switch coordinates DNA double-strand break repair pathway choice",

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.",

author = "Pai, {Chen Chun} and Deegan, {Rachel S.} and Lakxmi Subramanian and Csenge Gal and Sovan Sarkar and Blaikley, {Elizabeth J.} and Carol Walker and Lydia Hulme and Eric Bernhard and Sandra Codlin and J{\"u}rg B{\"a}hler and Robin Allshire and Simon Whitehall and Humphrey, {Timothy C.}",

year = "2014",

month = jun,

day = "9",

doi = "10.1038/ncomms5091",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - A histone H3K36 chromatin switch coordinates DNA double-strand break repair pathway choice

AU - Pai, Chen Chun

AU - Deegan, Rachel S.

AU - Subramanian, Lakxmi

AU - Gal, Csenge

AU - Sarkar, Sovan

AU - Blaikley, Elizabeth J.

AU - Walker, Carol

AU - Hulme, Lydia

AU - Bernhard, Eric

AU - Codlin, Sandra

AU - Bähler, Jürg

AU - Allshire, Robin

AU - Whitehall, Simon

AU - Humphrey, Timothy C.

PY - 2014/6/9

Y1 - 2014/6/9

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms5091

DO - 10.1038/ncomms5091

M3 - Article

AN - SCOPUS:84902251340

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 4091

ER -

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

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