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The budding yeast GSK-3 homologue Mck1 is an essential component of the spindle position checkpoint

The spindle position checkpoint (SPOC) is a mitotic surveillance mechanism in Saccharomyces cerevisiae that prevents cells from completing mitosis in response to spindle misalignment, thereby contributing to genomic integrity. The kinase Kin4, one of the most downstream SPOC components, is essential...

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Detalles Bibliográficos
Autores principales: Rathi, Siddhi, Polat, Irem, Pereira, Gislene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627454/
https://www.ncbi.nlm.nih.gov/pubmed/36321416
http://dx.doi.org/10.1098/rsob.220203
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author Rathi, Siddhi
Polat, Irem
Pereira, Gislene
author_facet Rathi, Siddhi
Polat, Irem
Pereira, Gislene
author_sort Rathi, Siddhi
collection PubMed
description The spindle position checkpoint (SPOC) is a mitotic surveillance mechanism in Saccharomyces cerevisiae that prevents cells from completing mitosis in response to spindle misalignment, thereby contributing to genomic integrity. The kinase Kin4, one of the most downstream SPOC components, is essential to stop the mitotic exit network (MEN), a signalling pathway that promotes the exit from mitosis and cell division. Previous work, however, suggested that a Kin4-independent pathway contributes to SPOC, yet the underlying mechanisms remain elusive. Here, we established the glycogen-synthase-kinase-3 (GSK-3) homologue Mck1, as a novel component that works independently of Kin4 to engage SPOC. Our data indicate that both Kin4 and Mck1 work in parallel to counteract MEN activation by the Cdc14 early anaphase release (FEAR) network. We show that Mck1's function in SPOC is mediated by the pre-replication complex protein and mitotic cyclin-dependent kinase (M-Cdk) inhibitor, Cdc6, which is degraded in a Mck1-dependent manner prior to mitosis. Moderate overproduction of Cdc6 phenocopies MCK1 deletion and causes SPOC deficiency via its N-terminal, M-Cdk inhibitory domain. Our data uncover an unprecedented role of GSK-3 kinases in coordinating spindle orientation with cell cycle progression.
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spelling pubmed-96274542022-11-07 The budding yeast GSK-3 homologue Mck1 is an essential component of the spindle position checkpoint Rathi, Siddhi Polat, Irem Pereira, Gislene Open Biol Research The spindle position checkpoint (SPOC) is a mitotic surveillance mechanism in Saccharomyces cerevisiae that prevents cells from completing mitosis in response to spindle misalignment, thereby contributing to genomic integrity. The kinase Kin4, one of the most downstream SPOC components, is essential to stop the mitotic exit network (MEN), a signalling pathway that promotes the exit from mitosis and cell division. Previous work, however, suggested that a Kin4-independent pathway contributes to SPOC, yet the underlying mechanisms remain elusive. Here, we established the glycogen-synthase-kinase-3 (GSK-3) homologue Mck1, as a novel component that works independently of Kin4 to engage SPOC. Our data indicate that both Kin4 and Mck1 work in parallel to counteract MEN activation by the Cdc14 early anaphase release (FEAR) network. We show that Mck1's function in SPOC is mediated by the pre-replication complex protein and mitotic cyclin-dependent kinase (M-Cdk) inhibitor, Cdc6, which is degraded in a Mck1-dependent manner prior to mitosis. Moderate overproduction of Cdc6 phenocopies MCK1 deletion and causes SPOC deficiency via its N-terminal, M-Cdk inhibitory domain. Our data uncover an unprecedented role of GSK-3 kinases in coordinating spindle orientation with cell cycle progression. The Royal Society 2022-11-02 /pmc/articles/PMC9627454/ /pubmed/36321416 http://dx.doi.org/10.1098/rsob.220203 Text en © 2022 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Rathi, Siddhi
Polat, Irem
Pereira, Gislene
The budding yeast GSK-3 homologue Mck1 is an essential component of the spindle position checkpoint
title The budding yeast GSK-3 homologue Mck1 is an essential component of the spindle position checkpoint
title_full The budding yeast GSK-3 homologue Mck1 is an essential component of the spindle position checkpoint
title_fullStr The budding yeast GSK-3 homologue Mck1 is an essential component of the spindle position checkpoint
title_full_unstemmed The budding yeast GSK-3 homologue Mck1 is an essential component of the spindle position checkpoint
title_short The budding yeast GSK-3 homologue Mck1 is an essential component of the spindle position checkpoint
title_sort budding yeast gsk-3 homologue mck1 is an essential component of the spindle position checkpoint
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627454/
https://www.ncbi.nlm.nih.gov/pubmed/36321416
http://dx.doi.org/10.1098/rsob.220203
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