Reference - Detail
| RRC ID | 48829 |
|---|---|
| Author | Amendola PG, Zaghet N, Ramalho JJ, Vilstrup Johansen J, Boxem M, Salcini AE. |
| Title | JMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity. |
| Journal | 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. |
| Volume | 13(2) |
| Pages | e1006632 |
| Published | 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 |
| Times Cited | 14 |
| WOS Category | GENETICS & HEREDITY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 8 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm3735 |