SGO2 does not play an essential role in separase inhibition during meiosis I in mouse oocytes.

During meiosis I in oocytes, anaphase is triggered by deactivation of cyclin B1-CDK1 and activation of separase. Active separase plays an essential role in cleaving cohesin rings that hold homologous chromosomes together. Critically, separase must be inhibited until all chromosomes are aligned and t...

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Main Authors: Benjamin Wetherall, David Bulmer, Alexandra Sarginson, Christopher Thomas, Suzanne Madgwick
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-04-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3003131
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author Benjamin Wetherall
David Bulmer
Alexandra Sarginson
Christopher Thomas
Suzanne Madgwick
author_facet Benjamin Wetherall
David Bulmer
Alexandra Sarginson
Christopher Thomas
Suzanne Madgwick
author_sort Benjamin Wetherall
collection DOAJ
description During meiosis I in oocytes, anaphase is triggered by deactivation of cyclin B1-CDK1 and activation of separase. Active separase plays an essential role in cleaving cohesin rings that hold homologous chromosomes together. Critically, separase must be inhibited until all chromosomes are aligned and the cell is prepared for anaphase I. Inhibition can be mediated through the binding of separase to either securin or cyclin B1-CDK1. The relative contribution of each inhibitory pathway varies depending on cell type. Recently, shugoshin-2 (SGO2) has also been shown to inhibit separase in mitotic cells. Here, we used a separase biosensor and perturbed the three inhibitory pathways during meiosis I in mouse oocytes. We show that inhibition mediated by either securin or cyclin B1-CDK1, but not SGO2, is independently sufficient to suppress separase activity. However, when both the securin and cyclin B1-CDK1 inhibitory pathways are perturbed together, separase activity begins prematurely, resulting in gross segregation defects. Furthermore, we characterized SGO2 destruction dynamics and concluded that it is not an essential separase inhibitor in mouse oocytes. The existence of multiple separase inhibitory pathways highlights the critical importance of tightly regulated separase activity during this unique and challenging cell division.
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spelling doaj-art-48b2e6c5d0b643eca5747709f94c6e672025-08-20T03:31:11ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852025-04-01234e300313110.1371/journal.pbio.3003131SGO2 does not play an essential role in separase inhibition during meiosis I in mouse oocytes.Benjamin WetherallDavid BulmerAlexandra SarginsonChristopher ThomasSuzanne MadgwickDuring meiosis I in oocytes, anaphase is triggered by deactivation of cyclin B1-CDK1 and activation of separase. Active separase plays an essential role in cleaving cohesin rings that hold homologous chromosomes together. Critically, separase must be inhibited until all chromosomes are aligned and the cell is prepared for anaphase I. Inhibition can be mediated through the binding of separase to either securin or cyclin B1-CDK1. The relative contribution of each inhibitory pathway varies depending on cell type. Recently, shugoshin-2 (SGO2) has also been shown to inhibit separase in mitotic cells. Here, we used a separase biosensor and perturbed the three inhibitory pathways during meiosis I in mouse oocytes. We show that inhibition mediated by either securin or cyclin B1-CDK1, but not SGO2, is independently sufficient to suppress separase activity. However, when both the securin and cyclin B1-CDK1 inhibitory pathways are perturbed together, separase activity begins prematurely, resulting in gross segregation defects. Furthermore, we characterized SGO2 destruction dynamics and concluded that it is not an essential separase inhibitor in mouse oocytes. The existence of multiple separase inhibitory pathways highlights the critical importance of tightly regulated separase activity during this unique and challenging cell division.https://doi.org/10.1371/journal.pbio.3003131
spellingShingle Benjamin Wetherall
David Bulmer
Alexandra Sarginson
Christopher Thomas
Suzanne Madgwick
SGO2 does not play an essential role in separase inhibition during meiosis I in mouse oocytes.
PLoS Biology
title SGO2 does not play an essential role in separase inhibition during meiosis I in mouse oocytes.
title_full SGO2 does not play an essential role in separase inhibition during meiosis I in mouse oocytes.
title_fullStr SGO2 does not play an essential role in separase inhibition during meiosis I in mouse oocytes.
title_full_unstemmed SGO2 does not play an essential role in separase inhibition during meiosis I in mouse oocytes.
title_short SGO2 does not play an essential role in separase inhibition during meiosis I in mouse oocytes.
title_sort sgo2 does not play an essential role in separase inhibition during meiosis i in mouse oocytes
url https://doi.org/10.1371/journal.pbio.3003131
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