An essential role of DmRad51/SpnA in DNA repair and meiotic checkpoint control

EMBO J. 2003 Nov 3;22(21):5863-74. doi: 10.1093/emboj/cdg564.

Abstract

Rad51 is a conserved protein essential for recombinational repair of double-stranded DNA breaks (DSBs) in somatic cells and during meiosis in germ cells. Yeast Rad51 mutants are viable but show meiosis defects. In the mouse, RAD51 deletions cause early embryonic death, suggesting that in higher eukaryotes Rad51 is required for viability. Here we report the identification of SpnA as the Drosophila Rad51 gene, whose sequence among the five known Drosophila Rad51-like genes is most closely related to the Rad51 homologs of human and yeast. DmRad51/spnA null mutants are viable but oogenesis is disrupted by the activation of a meiotic recombination checkpoint. We show that the meiotic phenotypes result from an inability to effectively repair DSBs. Our study further demonstrates that in Drosophila the Rad51-dependent homologous recombination pathway is not essential for DNA repair in the soma, unless exposed to DNA damaging agents. We therefore propose that under normal conditions a second, Rad51-independent, repair pathway prevents the lethal effects of DNA damage.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • DNA Repair / genetics
  • DNA Repair / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Female
  • Genes, Insect
  • Male
  • Meiosis / genetics
  • Meiosis / physiology*
  • Mutation
  • Oocytes / cytology
  • Oocytes / metabolism
  • Oogenesis / genetics
  • Oogenesis / physiology
  • Phenotype
  • Rad51 Recombinase
  • Radiation Tolerance / genetics

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Rad51 Recombinase
  • spn-A protein, Drosophila