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

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. © 2017 amendola et al.