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Proc Natl Acad Sci U S A ; 108(31): 12805-10, 2011 Aug 02.
Article in English | MEDLINE | ID: mdl-21768382

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.


Subject(s)
Caenorhabditis elegans Proteins/genetics , DNA Repair , Meiosis/genetics , Oxidoreductases, N-Demethylating/genetics , Animals , Animals, Genetically Modified , Antineoplastic Agents, Phytogenic/toxicity , Apoptosis/genetics , Blotting, Western , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/metabolism , Camptothecin/toxicity , DNA Breaks, Double-Stranded/drug effects , DNA Breaks, Double-Stranded/radiation effects , Gene Expression Profiling , Germ Cells/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Histones/metabolism , Lysine/metabolism , Methylation , Microscopy, Fluorescence , Mutation , Oligonucleotide Array Sequence Analysis , Oxidoreductases, N-Demethylating/metabolism , RNA Interference , Rad51 Recombinase/genetics , Rad51 Recombinase/metabolism , Reverse Transcriptase Polymerase Chain Reaction
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