RRC ID 48829
著者 Amendola PG, Zaghet N, Ramalho JJ, Vilstrup Johansen J, Boxem M, Salcini AE.
タイトル JMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity.
ジャーナル PLoS Genet
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.
巻・号 13(2)
ページ e1006632
公開日 2017-2-1
DOI 10.1371/journal.pgen.1006632
PII PGENETICS-D-16-01976
PMID 28207814
PMC PMC5336306
MeSH Animals Apoptosis / genetics Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Chromatin / genetics DNA Damage / genetics DNA Helicases / genetics* DNA Helicases / metabolism DNA Methylation / genetics DNA Repair / genetics DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Genomic Instability Germ Cells Histone-Lysine N-Methyltransferase / genetics Histones / genetics Homologous Recombination / genetics* Jumonji Domain-Containing Histone Demethylases / genetics* Jumonji Domain-Containing Histone Demethylases / metabolism Protein Processing, Post-Translational / genetics Rad51 Recombinase / genetics* Rad51 Recombinase / metabolism
IF 5.175
引用数 14
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm3735