| 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
|
| Resource |
| C.elegans |
tm3735 |
