The GATOR complex regulates an essential response to meiotic double-stranded breaks in Drosophila
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-stran...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
eLife Sciences Publications Ltd
2019-10-01
|
Series: | eLife |
Subjects: | |
Online Access: | https://elifesciences.org/articles/42149 |
_version_ | 1818027069233168384 |
---|---|
author | Youheng Wei Lucia Bettedi Chun-Yuan Ting Kuikwon Kim Yingbiao Zhang Jiadong Cai Mary A Lilly |
author_facet | Youheng Wei Lucia Bettedi Chun-Yuan Ting Kuikwon Kim Yingbiao Zhang Jiadong Cai Mary A Lilly |
author_sort | Youheng Wei |
collection | DOAJ |
description | 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. |
first_indexed | 2024-12-10T04:42:02Z |
format | Article |
id | doaj.art-845611d125924fd595672482da8a1bc1 |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-12-10T04:42:02Z |
publishDate | 2019-10-01 |
publisher | eLife Sciences Publications Ltd |
record_format | Article |
series | eLife |
spelling | doaj.art-845611d125924fd595672482da8a1bc12022-12-22T02:01:51ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.42149The GATOR complex regulates an essential response to meiotic double-stranded breaks in DrosophilaYouheng Wei0Lucia Bettedi1Chun-Yuan Ting2https://orcid.org/0000-0002-2302-4203Kuikwon Kim3Yingbiao Zhang4Jiadong Cai5Mary A Lilly6https://orcid.org/0000-0003-1564-619XCell Biology and Neurobiology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States; College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, ChinaCell Biology and Neurobiology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesCell Biology and Neurobiology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesCell Biology and Neurobiology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesCell Biology and Neurobiology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesCollege of Bioscience and Biotechnology, Yangzhou University, Yangzhou, ChinaCell Biology and Neurobiology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesThe 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.https://elifesciences.org/articles/42149GATORTORC1meiosisdouble-stranded breaksretrotransposonoogenesis |
spellingShingle | Youheng Wei Lucia Bettedi Chun-Yuan Ting Kuikwon Kim Yingbiao Zhang Jiadong Cai Mary A Lilly The GATOR complex regulates an essential response to meiotic double-stranded breaks in Drosophila eLife GATOR TORC1 meiosis double-stranded breaks retrotransposon oogenesis |
title | The GATOR complex regulates an essential response to meiotic double-stranded breaks in Drosophila |
title_full | The GATOR complex regulates an essential response to meiotic double-stranded breaks in Drosophila |
title_fullStr | The GATOR complex regulates an essential response to meiotic double-stranded breaks in Drosophila |
title_full_unstemmed | The GATOR complex regulates an essential response to meiotic double-stranded breaks in Drosophila |
title_short | The GATOR complex regulates an essential response to meiotic double-stranded breaks in Drosophila |
title_sort | gator complex regulates an essential response to meiotic double stranded breaks in drosophila |
topic | GATOR TORC1 meiosis double-stranded breaks retrotransposon oogenesis |
url | https://elifesciences.org/articles/42149 |
work_keys_str_mv | AT youhengwei thegatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT luciabettedi thegatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT chunyuanting thegatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT kuikwonkim thegatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT yingbiaozhang thegatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT jiadongcai thegatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT maryalilly thegatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT youhengwei gatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT luciabettedi gatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT chunyuanting gatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT kuikwonkim gatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT yingbiaozhang gatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT jiadongcai gatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila AT maryalilly gatorcomplexregulatesanessentialresponsetomeioticdoublestrandedbreaksindrosophila |