Open AccessJMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity
Author(s) -
Pier Giorgio Amendola,
Nico Zaghet,
João J. Ramalho,
Jens Vilstrup Johansen,
Mike Boxem,
Anna Elisabetta Salcini
Publication year - 2017
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1006632
Subject(s) - biology , homologous recombination , chromatin , dna repair , histone , non homologous end joining , microbiology and biotechnology , genetics , dna
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.