SPR-5 is a histone H3K4 demethylase with a role in meiotic double-strand break repair

Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12805-10. doi: 10.1073/pnas.1102298108. Epub 2011 Jul 18.

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

  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

  • Antineoplastic Agents, Phytogenic
  • Caenorhabditis elegans Proteins
  • Histones
  • Green Fluorescent Proteins
  • Oxidoreductases, N-Demethylating
  • SPR-5 protein, C elegans
  • Rad51 Recombinase
  • rad-51 protein, C elegans
  • Lysine
  • Camptothecin