Activation of a meiotic checkpoint during Drosophila oogenesis regulates the translation of gurken through Chk2/Mnk

Uri Abdu, Michael Brodsky, Trudi Schüpbach

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

Background: During Drosophila oogenesis, unrepaired double-strand DNA breaks activate a mei-41-dependent meiotic checkpoint, which couples the progression through meiosis to specific developmental processes. This checkpoint affects the accumulation of Gurken protein, a transforming growth factor α-like signaling molecule, as well as the morphology of the oocyte nucleus. However, the components of this checkpoint in flies have not been completely elucidated. Results: We show that a mutation in the Drosophila Chk2 homolog (DmChk2/Mnk) suppresses the defects in the translation of gurken mRNA and also the defects in oocyte nuclear morphology. We also found that DmChk2 is phosphorylated in a mei-41-dependent pathway. Analysis of the meiotic cell cycle progression shows that the Drosophila Chk2 homolog is not required during early meiotic prophase, as has been observed for Chk2 in C. elegans. We demonstrate that the activation of the meiotic checkpoint affects Dwee1 localization and is associated with DmChk2-dependent posttranslational modification of Dwee1. We suggest that Dwee1 has a role in the meiotic checkpoint that regulates the meiotic cell cycle, but not the translation of gurken mRNA. In addition, we found that p53 and mus304, the Drosophila ATR-IP homolog, are not required for the patterning defects caused by the meiotic DNA repair mutations. Conclusions: DmChk2 is a transducer of the meiotic checkpoint in flies that is activated by unrepaired double-strand DNA breaks. Activation of DmChk2 in this specific checkpoint affects a cell cycle regulator as well as mRNA translation.

Original languageEnglish (US)
Pages (from-to)1645-1651
Number of pages7
JournalCurrent Biology
Volume12
Issue number19
DOIs
StatePublished - Oct 1 2002

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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