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

2018 ◽  
Author(s):  
Youheng Wei ◽  
Lucia Bettedi ◽  
Kuikwon Kim ◽  
Chun-Yuan Ting ◽  
Mary A. Lilly
Keyword(s):  
Metabolic Pathways ◽  
Growth Arrest ◽  
Meiotic Progression ◽  
Delayed Repair ◽  
Meiotic Dsbs ◽  
Female Germline ◽  
Dependent Pathway ◽  
Meiotic Entry

AbstractThe TORC1 inhibitor 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 report that the TORC1 regulators GATOR1 and GATOR2 mediate a response to meiotic double-stranded breaks (DSBs) during Drosophila oogenesis. We find that meiotic DSBs trigger the activation of a GATOR1 dependent pathway that downregulates TORC1 activity in the female germline. In GATOR1 mutants, high TORC1 activity results in the delayed repair of meiotic DSBs and the hyperactivation of p53. Conversely, the GATOR2 component Mio is required to attenuate GATOR1 activity, to ensure that meiotic DSBs do not trigger a permanent growth arrest. Unexpectedly, we found that GATOR1 inhibits retrotransposon expression in the presence of meiotic DSBs in a pathway that functions in parallel to p53. Our studies have revealed a link between the GATOR complex, the repair of meiotic DSBs and retrotransposon expression

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

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Youheng Wei ◽  
Lucia Bettedi ◽  
Chun-Yuan Ting ◽  
Kuikwon Kim ◽  
Yingbiao Zhang ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Oocyte Growth ◽  
Drosophila Oogenesis ◽  
Meiotic Progression ◽  
Delayed Repair ◽  
Meiotic Dsbs ◽  
Meiotic Entry

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.

scholarly journals Crossover Interference in Saccharomyces cerevisiae Requires a TID1/RDH54- and DMC1-Dependent Pathway

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1273-1286 ◽  
Author(s):  
Miki Shinohara ◽  
Kazuko Sakai ◽  
Akira Shinohara ◽  
Douglas K Bishop
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
Strand Break ◽  
Tetrad Analysis ◽  
Yeast Saccharomyces Cerevisiae ◽  
Crossover Interference ◽  
Meiotic Progression ◽  
Invasion Stage ◽  
Strand Invasion ◽  
Dependent Pathway

Abstract Two RecA-like recombinases, Rad51 and Dmc1, function together during double-strand break (DSB)-mediated meiotic recombination to promote homologous strand invasion in the budding yeast Saccharomyces cerevisiae. Two partially redundant proteins, Rad54 and Tid1/Rdh54, act as recombinase accessory factors. Here, tetrad analysis shows that mutants lacking Tid1 form four-viable-spore tetrads with levels of interhomolog crossover (CO) and noncrossover recombination similar to, or slightly greater than, those in wild type. Importantly, tid1 mutants show a marked defect in crossover interference, a mechanism that distributes crossover events nonrandomly along chromosomes during meiosis. Previous work showed that dmc1Δ mutants are strongly defective in strand invasion and meiotic progression and that these defects can be partially suppressed by increasing the copy number of RAD54. Tetrad analysis is used to show that meiotic recombination in RAD54-suppressed dmc1Δ cells is similar to that in tid1; the frequency of COs and gene conversions is near normal, but crossover interference is defective. These results support the proposal that crossover interference acts at the strand invasion stage of recombination.

scholarly journals A PKC-η/Fyn-Dependent Pathway Leading to Keratinocyte Growth Arrest and Differentiation

2000 ◽  
Vol 6 (5) ◽  
pp. 1121-1129 ◽  
Author(s):  
Sara Cabodi ◽  
Enzo Calautti ◽  
Claudio Talora ◽  
Toshio Kuroki ◽  
Paul L. Stein ◽  
...  
Keyword(s):  
Growth Arrest ◽  
Dependent Pathway

scholarly journals BCL6-mediated Attenuation of DNA Damage Sensing Triggers Growth Arrest and Senescence through a p53-dependent Pathway in a Cell Context-dependent Manner

2008 ◽  
Vol 283 (33) ◽  
pp. 22565-22572 ◽  
Author(s):  
Stella Maris Ranuncolo ◽  
Ling Wang ◽  
Jose M. Polo ◽  
Tania Dell'Oso ◽  
Jamil Dierov ◽  
...  
Keyword(s):  
Dna Damage ◽  
Growth Arrest ◽  
Dependent Manner ◽  
Damage Sensing ◽  
A Cell ◽  
Context Dependent ◽  
Dependent Pathway

scholarly journals Adipocyte Metabolic Pathways Regulated by Diet Control the Female Germline Stem Cell Lineage in Drosophila melanogaster

Genetics ◽  
2017 ◽  
Vol 206 (2) ◽  
pp. 953-971 ◽  
Author(s):  
Shinya Matsuoka ◽  
Alissa R. Armstrong ◽  
Leesa L. Sampson ◽  
Kaitlin M. Laws ◽  
Daniela Drummond-Barbosa
Keyword(s):  
Drosophila Melanogaster ◽  
Stem Cell ◽  
Metabolic Pathways ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Stem Cell Lineage ◽  
Diet Control ◽  
Female Germline

scholarly journals Spatio-temporal expression of ANK2 promotes cytokinesis in oocytes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna Tetkova ◽  
Denisa Jansova ◽  
Andrej Susor
Keyword(s):  
Nuclear Envelope ◽  
Regulation Of Gene Expression ◽  
Early Embryo ◽  
Temporal Expression ◽  
Nuclear Envelope Breakdown ◽  
Meiotic Progression ◽  
Maternal Transcripts ◽  
Specific Mrnas ◽  
Spatio Temporal ◽  
Dependent Pathway

Abstract In the absence of transcription, the regulation of gene expression in oocytes is controlled almost exclusively at the level of transcriptome and proteome stabilization, and translation. A subset of maternal transcripts is stored in a translationally dormant state in the oocyte, and temporally driven translation of specific mRNAs propel meiotic progression, oocyte-to-embryo transition and early embryo development. We identified Ank2.3 as the only transcript variant present in the mouse oocyte and discovered that it is translated after nuclear envelope breakdown. Here we show that Ank2.3 mRNA is localized in higher concentration in the oocyte nucleoplasm and, after nuclear envelope breakdown, in the newly forming spindle where its translation occurs. Furthermore, we reveal that Ank2.3 mRNA contains an oligo-pyrimidine motif at 5′UTR that predetermines its translation through a cap-dependent pathway. Lastly, we show that prevention of ANK2 translation leads to abnormalities in oocyte cytokinesis.

scholarly journals Activin A induces growth arrest through a SMAD- dependent pathway in hepatic progenitor cells

2014 ◽  
Vol 12 (1) ◽  
pp. 18 ◽  
Author(s):  
Lin Chen ◽  
Wei Zhang ◽  
Hui-fang Liang ◽  
Qiao-dan Zhou ◽  
Ze-yang Ding ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Growth Arrest ◽  
Activin A ◽  
Hepatic Progenitor Cells ◽  
Dependent Pathway

scholarly journals Interleukin-6 Mediates G0/G1 Growth Arrest in Hepatocellular Carcinoma Through a STAT 3-Dependent Pathway

2008 ◽  
Vol 147 (1) ◽  
pp. 23-33 ◽  
Author(s):  
Dairmuid M. Moran ◽  
M. Adrian Mattocks ◽  
Paul A. Cahill ◽  
Leonidas G. Koniaris ◽  
Iain H. McKillop
Keyword(s):  
Hepatocellular Carcinoma ◽  
Interleukin 6 ◽  
Growth Arrest ◽  
Dependent Pathway

scholarly journals Retinoblastoma gene product as a downstream target for a ceramide-dependent pathway of growth arrest.

1995 ◽  
Vol 92 (5) ◽  
pp. 1347-1351 ◽  
Author(s):  
G. S. Dbaibo ◽  
M. Y. Pushkareva ◽  
S. Jayadev ◽  
J. K. Schwarz ◽  
J. M. Horowitz ◽  
...  
Keyword(s):  
Gene Product ◽  
Growth Arrest ◽  
Retinoblastoma Gene ◽  
Downstream Target ◽  
Retinoblastoma Gene Product ◽  
Dependent Pathway
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