title: JMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity.
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.
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Pier Giorgio
authors.identifier: 0000-0002-1476-1287
authors.initials: PG
authors.lastname: Amendola
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nico
authors.initials: N
authors.lastname: Zaghet
authors.affiliation: Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, CH Utrecht, The Netherlands.
authors.forename: João J
authors.initials: JJ
authors.lastname: Ramalho
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Vilstrup Johansen
authors.affiliation: Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, CH Utrecht, The Netherlands.
authors.forename: Mike
authors.identifier: 0000-0003-3966-4173
authors.initials: M
authors.lastname: Boxem
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.|Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anna Elisabetta
authors.initials: AE
authors.lastname: Salcini
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D042822:Genomic Instability; D005854:Germ Cells; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006657:Histones / Q000235:genetics; D059765:Homologous Recombination / Q000235:genetics*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; C000602003:RFS-1 protein, C elegans; D056484:Jumonji Domain-Containing Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase; D051135:Rad51 Recombinase; C495148:rad-51 protein, C elegans; C547400:HELQ-1 protein, C elegans; C532891:rcq-5 protein, C elegans; D004265:DNA Helicases