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Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis
Here, we screened a 10,371 library of diverse molecules using a drug-sensitive fission yeast strain to identify compounds which cause defects in chromosome segregation during mitosis. We identified a phosphorium-ylide-based compound Cutin-1 which inhibits nuclear envelope expansion and nuclear elong...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813296/ https://www.ncbi.nlm.nih.gov/pubmed/26869222 http://dx.doi.org/10.1242/jcs.181560 |
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author | Takemoto, Ai Kawashima, Shigehiro A. Li, Juan-Juan Jeffery, Linda Yamatsugu, Kenzo Elemento, Olivier Nurse, Paul |
author_facet | Takemoto, Ai Kawashima, Shigehiro A. Li, Juan-Juan Jeffery, Linda Yamatsugu, Kenzo Elemento, Olivier Nurse, Paul |
author_sort | Takemoto, Ai |
collection | PubMed |
description | Here, we screened a 10,371 library of diverse molecules using a drug-sensitive fission yeast strain to identify compounds which cause defects in chromosome segregation during mitosis. We identified a phosphorium-ylide-based compound Cutin-1 which inhibits nuclear envelope expansion and nuclear elongation during the closed mitosis of fission yeast, and showed that its target is the β-subunit of fatty acid synthase. A point mutation in the dehydratase domain of Fas1 conferred in vivo and in vitro resistance to Cutin-1. Time-lapse photomicrography showed that the bulk of the chromosomes were only transiently separated during mitosis, and nucleoli separation was defective. Subsequently sister chromatids re-associated leading to chromosomal mis-segregation. These segregation defects were reduced when the nuclear volume was increased and were increased when the nuclear volume was reduced. We propose that there needs to be sufficient nuclear volume to allow the nuclear elongation necessary during a closed mitosis to take place for proper chromosome segregation, and that inhibition of fatty acid synthase compromises nuclear elongation and leads to defects in chromosomal segregation. |
format | Online Article Text |
id | pubmed-4813296 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-48132962016-04-20 Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis Takemoto, Ai Kawashima, Shigehiro A. Li, Juan-Juan Jeffery, Linda Yamatsugu, Kenzo Elemento, Olivier Nurse, Paul J Cell Sci Research Article Here, we screened a 10,371 library of diverse molecules using a drug-sensitive fission yeast strain to identify compounds which cause defects in chromosome segregation during mitosis. We identified a phosphorium-ylide-based compound Cutin-1 which inhibits nuclear envelope expansion and nuclear elongation during the closed mitosis of fission yeast, and showed that its target is the β-subunit of fatty acid synthase. A point mutation in the dehydratase domain of Fas1 conferred in vivo and in vitro resistance to Cutin-1. Time-lapse photomicrography showed that the bulk of the chromosomes were only transiently separated during mitosis, and nucleoli separation was defective. Subsequently sister chromatids re-associated leading to chromosomal mis-segregation. These segregation defects were reduced when the nuclear volume was increased and were increased when the nuclear volume was reduced. We propose that there needs to be sufficient nuclear volume to allow the nuclear elongation necessary during a closed mitosis to take place for proper chromosome segregation, and that inhibition of fatty acid synthase compromises nuclear elongation and leads to defects in chromosomal segregation. The Company of Biologists Ltd 2016-03-15 /pmc/articles/PMC4813296/ /pubmed/26869222 http://dx.doi.org/10.1242/jcs.181560 Text en © 2016. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Takemoto, Ai Kawashima, Shigehiro A. Li, Juan-Juan Jeffery, Linda Yamatsugu, Kenzo Elemento, Olivier Nurse, Paul Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis |
title | Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis |
title_full | Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis |
title_fullStr | Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis |
title_full_unstemmed | Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis |
title_short | Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis |
title_sort | nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813296/ https://www.ncbi.nlm.nih.gov/pubmed/26869222 http://dx.doi.org/10.1242/jcs.181560 |
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