The GATOR complex regulates an essential response to meiotic double-stranded breaks in Drosophila

  1. Youheng Wei
  2. Lucia Bettedi
  3. Chun-Yuan Ting
  4. Kuikwon Kim
  5. Yingbiao Zhang
  6. Jiadong Cai
  7. Mary A Lilly  Is a corresponding author
  1. National Institute of Child Health and Human Development, National Institutes of Health, United States
  2. Yangzhou University, China

Abstract

The TORC1 regulator GATOR1/SEACIT controls meiotic entry and early meiotic events in yeast. However, how metabolic pathways influence meiotic progression in metazoans remains poorly understood. Here we examine the role of the TORC1 regulators GATOR1 and GATOR2 in the response to meiotic double-stranded breaks (DSB) during Drosophila oogenesis. We find that in mutants of the GATOR2 component mio, meiotic DSBs trigger the constitutive downregulation of TORC1 activity and a permanent arrest in oocyte growth. Conversely, in GATOR1 mutants, high TORC1 activity results in the delayed repair of meiotic DSBs and the hyperactivation of p53. Unexpectedly, we found that GATOR1 inhibits retrotransposon expression in the presence of meiotic DSBs in a pathway that functions in parallel to p53. Thus, our studies have revealed a link between oocyte metabolism, the repair of meiotic DSBs and retrotransposon expression.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Author details

  1. Youheng Wei

    Cell Biology and Structural Biology Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Lucia Bettedi

    Cell Biology and Structural Biology Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Chun-Yuan Ting

    Cell Biology and Structural Biology Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2302-4203
  4. Kuikwon Kim

    Cell Biology and Structural Biology Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yingbiao Zhang

    Cell Biology and Structural Biology Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jiadong Cai

    College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Mary A Lilly

    Cell Biology and Structural Biology Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    For correspondence
    lillym@helix.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1564-619X

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (Intramural Program HD00163 16)

  • Mary A Lilly

National Science Foundation of Jiangsu Province (BK20181456)

  • Youheng Wei

National Natural Science Foundation of China (31872287)

  • Youheng Wei

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Youheng Wei
  2. Lucia Bettedi
  3. Chun-Yuan Ting
  4. Kuikwon Kim
  5. Yingbiao Zhang
  6. Jiadong Cai
  7. Mary A Lilly
(2019)
The GATOR complex regulates an essential response to meiotic double-stranded breaks in Drosophila
eLife 8:e42149.
https://doi.org/10.7554/eLife.42149

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https://doi.org/10.7554/eLife.42149