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PLoS Genet. 2017 Feb 16;13(2):e1006632. doi: 10.1371/journal.pgen.1006632. eCollection 2017 Feb.

JMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity.

Author information

1
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
2
Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
3
Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, CH Utrecht, The Netherlands.

Abstract

The eukaryotic genome is organized in a three-dimensional structure called chromatin, constituted by DNA and associated proteins, the majority of which are histones. Post-translational modifications of histone proteins greatly influence chromatin structure and regulate many DNA-based biological processes. Methylation of lysine 36 of histone 3 (H3K36) is a post-translational modification functionally relevant during early steps of DNA damage repair. Here, we show that the JMJD-5 regulates H3K36 di-methylation and it is required at late stages of double strand break repair mediated by homologous recombination. Loss of jmjd-5 results in hypersensitivity to ionizing radiation and in meiotic defects, and it is associated with aberrant retention of RAD-51 at sites of double strand breaks. Analyses of jmjd-5 genetic interactions with genes required for resolving recombination intermediates (rtel-1) or promoting the resolution of RAD-51 double stranded DNA filaments (rfs-1 and helq-1) suggest that jmjd-5 prevents the formation of stalled postsynaptic recombination intermediates and favors RAD-51 removal. As these phenotypes are all recapitulated by a catalytically inactive jmjd-5 mutant, we propose a novel role for H3K36me2 regulation during late steps of homologous recombination critical to preserve genome integrity.

PMID:
28207814
PMCID:
PMC5336306
DOI:
10.1371/journal.pgen.1006632
[Indexed for MEDLINE]
Free PMC Article

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