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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Animals, Genetically Modified
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Antineoplastic Agents, Phytogenic / toxicity
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Apoptosis / genetics
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Blotting, Western
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins / genetics*
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Caenorhabditis elegans Proteins / metabolism
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Camptothecin / toxicity
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DNA Breaks, Double-Stranded / drug effects
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DNA Breaks, Double-Stranded / radiation effects
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DNA Repair*
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Gene Expression Profiling
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Germ Cells / metabolism
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Histones / metabolism
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Lysine / metabolism
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Meiosis / genetics*
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Methylation
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Microscopy, Fluorescence
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Mutation
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Oligonucleotide Array Sequence Analysis
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Oxidoreductases, N-Demethylating / genetics*
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Oxidoreductases, N-Demethylating / metabolism
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RNA Interference
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Rad51 Recombinase / genetics
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Rad51 Recombinase / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Antineoplastic Agents, Phytogenic
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Caenorhabditis elegans Proteins
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Histones
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Green Fluorescent Proteins
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Oxidoreductases, N-Demethylating
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SPR-5 protein, C elegans
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Rad51 Recombinase
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rad-51 protein, C elegans
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Lysine
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Camptothecin