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Activation of a meiotic checkpoint regulates translation of Gurken during Drosophila oogenesis

Abstract

The genes okra and spindle-B act during meiosis in Drosophila to repair double-stranded DNA breaks (DSBs) associated with meiotic recombination. Unexpectedly, mutations in these genes cause dorsoventral patterning defects during oogenesis. These defects result from a failure to accumulate Gurken protein, which is required to initiate dorsoventral patterning during oogenesis. Here we find that the block in Gurken accumulation in the oocyte cytoplasm reflects activation of a meiotic checkpoint in response to the persistence of DSBs in the nucleus. We also show that Vasa is a target of this meiotic checkpoint, and so may mediate the checkpoint-dependent translational regulation of Gurken.

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Figure 1: Competitive PCR analysis of grk mRNA levels.
Figure 2: Confocal analysis of karyosome morphology and Grk accumulation in wild-type and mutant Drosophila egg chambers.
Figure 3: Western blots of Vasa protein in wild-type and mutant ovarian extracts.
Figure 4: Model for the checkpoint-mediated coupling of meiosis to translation of Gurken.

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Acknowledgements

We thank K. McKim, J. Sekelsky, S. Hawley, S. Wayson and R. Ray for mutant stocks and helpful discussions; C. VanBuskirk for sharing anti-Grk monoclonal antibodies; I. Clark for Vasa reagents and advice on Vasa westerns; G. Shanower, G. Deshpande and P. Schedl for their advice; and E. Wieschaus, L. Nilson, C. VanBuskirk and A. Norvell for comments on the manuscript. This work was supported by the US Public Health Service grant PO1 CA 41086 and the HHMI.

Correspondence and requests for materials should be addressed to T.S.

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Correspondence to Trudi Schüpbach.

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Ghabrial, A., Schüpbach, T. Activation of a meiotic checkpoint regulates translation of Gurken during Drosophila oogenesis. Nat Cell Biol 1, 354–357 (1999). https://doi.org/10.1038/14046

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