title: SPR-5 is a histone H3K4 demethylase with a role in meiotic double-strand break repair.
abstract: Regulation of histone methylation levels has long been implicated in multiple cellular processes, many of which involve transcription. Here, however, we report a unique role for the Caenorhabditis elegans histone demethylase SPR-5 in meiotic DNA double-strand break repair (DSBR). SPR-5 shows enzymatic activity toward H3K4me2 both in vitro and in the nematode germline, and spr-5 mutants show several phenotypes indicating a perturbation of DSBR, including increased p53-dependent germ cell apoptosis, increased levels of the DSBR marker RAD-51, and sensitivity toward DSB-inducing treatments. spr-5 mutants show no transcriptional misregulation of known DSBR involved genes. Instead, SPR-5 shows a rapid subcellular relocalization upon DSB-inducing treatment, which suggests that SPR-5 may function directly in DSBR.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Nottke
authors.forename: Sara E
authors.initials: SE
authors.lastname: Beese-Sims
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Pantalena
authors.forename: Valerie
authors.initials: V
authors.lastname: Reinke
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.forename: Monica P
authors.initials: MP
authors.lastname: Colaiácovo
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002166:Camptothecin / Q000633:toxicity; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair; D020869:Gene Expression Profiling; D005854:Germ Cells / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008540:Meiosis / Q000235:genetics*; D008745:Methylation; D008856:Microscopy, Fluorescence; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D029742:Caenorhabditis elegans Proteins; D006657:Histones; D049452:Green Fluorescent Proteins; D010089:Oxidoreductases, N-Demethylating; C468848:SPR-5 protein, C elegans; D051135:Rad51 Recombinase; C495148:rad-51 protein, C elegans; D008239:Lysine; D002166:Camptothecin