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Relief of the Dma1-mediated checkpoint requires Dma1 autoubiquitination and dynamic localization
Chromosome segregation and cell division are coupled to prevent aneuploidy and cell death. In the fission yeast Schizosaccharomyces pombe, the septation initiation network (SIN) promotes cytokinesis, but upon mitotic checkpoint activation, the SIN is actively inhibited to prevent cytokinesis from oc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249794/ https://www.ncbi.nlm.nih.gov/pubmed/29975113 http://dx.doi.org/10.1091/mbc.E18-04-0261 |
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author | Jones, Christine M. Chen, Jun-Song Johnson, Alyssa E. Elmore, Zachary C. Cullati, Sierra N. Beckley, Janel R. Gould, Kathleen L. |
author_facet | Jones, Christine M. Chen, Jun-Song Johnson, Alyssa E. Elmore, Zachary C. Cullati, Sierra N. Beckley, Janel R. Gould, Kathleen L. |
author_sort | Jones, Christine M. |
collection | PubMed |
description | Chromosome segregation and cell division are coupled to prevent aneuploidy and cell death. In the fission yeast Schizosaccharomyces pombe, the septation initiation network (SIN) promotes cytokinesis, but upon mitotic checkpoint activation, the SIN is actively inhibited to prevent cytokinesis from occurring before chromosomes have safely segregated. SIN inhibition during the mitotic checkpoint is mediated by the E3 ubiquitin ligase Dma1. Dma1 binds to the CK1-phosphorylated SIN scaffold protein Sid4 at the spindle pole body (SPB), and ubiquitinates it. Sid4 ubiquitination antagonizes the SPB localization of the Pololike kinase Plo1, the major SIN activator, so that SIN signaling is delayed. How this checkpoint is silenced once spindle defects are resolved has not been clear. Here we establish that Dma1 transiently leaves SPBs during anaphase B due to extensive autoubiquitination. The SIN is required for Dma1 to return to SPBs later in anaphase. Blocking Dma1 removal from SPBs by permanently tethering it to Sid4 prevents SIN activation and cytokinesis. Therefore, controlling Dma1’s SPB dynamics in anaphase is an essential step in S. pombe cell division and the silencing of the Dma1-dependent mitotic checkpoint. |
format | Online Article Text |
id | pubmed-6249794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-62497942018-11-23 Relief of the Dma1-mediated checkpoint requires Dma1 autoubiquitination and dynamic localization Jones, Christine M. Chen, Jun-Song Johnson, Alyssa E. Elmore, Zachary C. Cullati, Sierra N. Beckley, Janel R. Gould, Kathleen L. Mol Biol Cell Article Chromosome segregation and cell division are coupled to prevent aneuploidy and cell death. In the fission yeast Schizosaccharomyces pombe, the septation initiation network (SIN) promotes cytokinesis, but upon mitotic checkpoint activation, the SIN is actively inhibited to prevent cytokinesis from occurring before chromosomes have safely segregated. SIN inhibition during the mitotic checkpoint is mediated by the E3 ubiquitin ligase Dma1. Dma1 binds to the CK1-phosphorylated SIN scaffold protein Sid4 at the spindle pole body (SPB), and ubiquitinates it. Sid4 ubiquitination antagonizes the SPB localization of the Pololike kinase Plo1, the major SIN activator, so that SIN signaling is delayed. How this checkpoint is silenced once spindle defects are resolved has not been clear. Here we establish that Dma1 transiently leaves SPBs during anaphase B due to extensive autoubiquitination. The SIN is required for Dma1 to return to SPBs later in anaphase. Blocking Dma1 removal from SPBs by permanently tethering it to Sid4 prevents SIN activation and cytokinesis. Therefore, controlling Dma1’s SPB dynamics in anaphase is an essential step in S. pombe cell division and the silencing of the Dma1-dependent mitotic checkpoint. The American Society for Cell Biology 2018-09-01 /pmc/articles/PMC6249794/ /pubmed/29975113 http://dx.doi.org/10.1091/mbc.E18-04-0261 Text en © 2018 Jones, Chen, et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Article Jones, Christine M. Chen, Jun-Song Johnson, Alyssa E. Elmore, Zachary C. Cullati, Sierra N. Beckley, Janel R. Gould, Kathleen L. Relief of the Dma1-mediated checkpoint requires Dma1 autoubiquitination and dynamic localization |
title | Relief of the Dma1-mediated checkpoint requires Dma1 autoubiquitination and dynamic localization |
title_full | Relief of the Dma1-mediated checkpoint requires Dma1 autoubiquitination and dynamic localization |
title_fullStr | Relief of the Dma1-mediated checkpoint requires Dma1 autoubiquitination and dynamic localization |
title_full_unstemmed | Relief of the Dma1-mediated checkpoint requires Dma1 autoubiquitination and dynamic localization |
title_short | Relief of the Dma1-mediated checkpoint requires Dma1 autoubiquitination and dynamic localization |
title_sort | relief of the dma1-mediated checkpoint requires dma1 autoubiquitination and dynamic localization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249794/ https://www.ncbi.nlm.nih.gov/pubmed/29975113 http://dx.doi.org/10.1091/mbc.E18-04-0261 |
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