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...

Full description

Bibliographic Details
Main Authors: Youheng Wei, Lucia Bettedi, Chun-Yuan Ting, Kuikwon Kim, Yingbiao Zhang, Jiadong Cai, Mary A Lilly
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