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Ubc1 turnover contributes to the spindle assembly checkpoint in Saccharomyces cerevisiae

The spindle assembly checkpoint protects the integrity of the genome by ensuring that chromosomes are properly attached to the mitotic spindle before they are segregated during anaphase. Activation of the spindle checkpoint results in inhibition of the Anaphase-Promoting Complex (APC), an E3 ubiquit...

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Autores principales: Arsenault, Heather E, Ghizzoni, Julie M, Leech, Cassandra M, Diers, Anne R, Gesta, Stephane, Vishnudas, Vivek K, Narain, Niven R, Sarangarajan, Rangaprasad, Benanti, Jennifer A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664427/
https://www.ncbi.nlm.nih.gov/pubmed/34586382
http://dx.doi.org/10.1093/g3journal/jkab346
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author Arsenault, Heather E
Ghizzoni, Julie M
Leech, Cassandra M
Diers, Anne R
Gesta, Stephane
Vishnudas, Vivek K
Narain, Niven R
Sarangarajan, Rangaprasad
Benanti, Jennifer A
author_facet Arsenault, Heather E
Ghizzoni, Julie M
Leech, Cassandra M
Diers, Anne R
Gesta, Stephane
Vishnudas, Vivek K
Narain, Niven R
Sarangarajan, Rangaprasad
Benanti, Jennifer A
author_sort Arsenault, Heather E
collection PubMed
description The spindle assembly checkpoint protects the integrity of the genome by ensuring that chromosomes are properly attached to the mitotic spindle before they are segregated during anaphase. Activation of the spindle checkpoint results in inhibition of the Anaphase-Promoting Complex (APC), an E3 ubiquitin ligase that triggers the metaphase–anaphase transition. Here, we show that levels of Ubc1, an E2 enzyme that functions in complex with the APC, modulate the response to spindle checkpoint activation in Saccharomyces cerevisiae. Overexpression of Ubc1 increased resistance to microtubule poisons, whereas Ubc1 shut-off sensitized cells. We also found that Ubc1 levels are regulated by the spindle checkpoint. Checkpoint activation or direct APC inhibition led to a decrease in Ubc1 levels, charging, and half-life. Additionally, stabilization of Ubc1 prevented its down-regulation by the spindle checkpoint and increased resistance to checkpoint-activating drugs. These results suggest that down-regulation of Ubc1 in response to spindle checkpoint signaling is necessary for a robust cell cycle arrest.
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spelling pubmed-86644272021-12-13 Ubc1 turnover contributes to the spindle assembly checkpoint in Saccharomyces cerevisiae Arsenault, Heather E Ghizzoni, Julie M Leech, Cassandra M Diers, Anne R Gesta, Stephane Vishnudas, Vivek K Narain, Niven R Sarangarajan, Rangaprasad Benanti, Jennifer A G3 (Bethesda) Investigation The spindle assembly checkpoint protects the integrity of the genome by ensuring that chromosomes are properly attached to the mitotic spindle before they are segregated during anaphase. Activation of the spindle checkpoint results in inhibition of the Anaphase-Promoting Complex (APC), an E3 ubiquitin ligase that triggers the metaphase–anaphase transition. Here, we show that levels of Ubc1, an E2 enzyme that functions in complex with the APC, modulate the response to spindle checkpoint activation in Saccharomyces cerevisiae. Overexpression of Ubc1 increased resistance to microtubule poisons, whereas Ubc1 shut-off sensitized cells. We also found that Ubc1 levels are regulated by the spindle checkpoint. Checkpoint activation or direct APC inhibition led to a decrease in Ubc1 levels, charging, and half-life. Additionally, stabilization of Ubc1 prevented its down-regulation by the spindle checkpoint and increased resistance to checkpoint-activating drugs. These results suggest that down-regulation of Ubc1 in response to spindle checkpoint signaling is necessary for a robust cell cycle arrest. Oxford University Press 2021-09-29 /pmc/articles/PMC8664427/ /pubmed/34586382 http://dx.doi.org/10.1093/g3journal/jkab346 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigation
Arsenault, Heather E
Ghizzoni, Julie M
Leech, Cassandra M
Diers, Anne R
Gesta, Stephane
Vishnudas, Vivek K
Narain, Niven R
Sarangarajan, Rangaprasad
Benanti, Jennifer A
Ubc1 turnover contributes to the spindle assembly checkpoint in Saccharomyces cerevisiae
title Ubc1 turnover contributes to the spindle assembly checkpoint in Saccharomyces cerevisiae
title_full Ubc1 turnover contributes to the spindle assembly checkpoint in Saccharomyces cerevisiae
title_fullStr Ubc1 turnover contributes to the spindle assembly checkpoint in Saccharomyces cerevisiae
title_full_unstemmed Ubc1 turnover contributes to the spindle assembly checkpoint in Saccharomyces cerevisiae
title_short Ubc1 turnover contributes to the spindle assembly checkpoint in Saccharomyces cerevisiae
title_sort ubc1 turnover contributes to the spindle assembly checkpoint in saccharomyces cerevisiae
topic Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664427/
https://www.ncbi.nlm.nih.gov/pubmed/34586382
http://dx.doi.org/10.1093/g3journal/jkab346
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