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

• Published in: PLoS genetics Vol. 13; no. 2; p. e1006632
• Main Authors: Amendola, Pier Giorgio, Zaghet, Nico, Ramalho, João J., Vilstrup Johansen, Jens, Boxem, Mike, Salcini, Anna Elisabetta
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.02.2017; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Apoptosis - genetics; Biology and life sciences; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Chromatin; Chromatin - genetics; Chromosomes; Colleges & universities; Deoxyribonucleic acid; Developmental biology; DNA; DNA damage; DNA Damage - genetics; DNA Helicases - genetics; DNA Helicases - metabolism; DNA methylation; DNA Methylation - genetics; DNA repair; DNA Repair - genetics; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epigenetics; Funding; Genes; Genetic regulation; Genomes; Genomic Instability; Germ Cells; Histone-Lysine N-Methyltransferase - genetics; Histones - genetics; Homologous Recombination - genetics; Ionizing radiation; Jumonji Domain-Containing Histone Demethylases - genetics; Jumonji Domain-Containing Histone Demethylases - metabolism; People and Places; Post-translational modifications; Protein Processing, Post-Translational - genetics; Proteins; Rad51 Recombinase - genetics; Rad51 Recombinase - metabolism; United States; Denmark
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006632

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.