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Timing of centrosome separation is important for accurate chromosome segregation
Spindle assembly, establishment of kinetochore attachment, and sister chromatid separation must occur during mitosis in a highly coordinated fashion to ensure accurate chromosome segregation. In most vertebrate cells, the nuclear envelope must break down to allow interaction between microtubules of...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268720/ https://www.ncbi.nlm.nih.gov/pubmed/22130796 http://dx.doi.org/10.1091/mbc.E11-02-0095 |
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author | Silkworth, William T. Nardi, Isaac K. Paul, Raja Mogilner, Alex Cimini, Daniela |
author_facet | Silkworth, William T. Nardi, Isaac K. Paul, Raja Mogilner, Alex Cimini, Daniela |
author_sort | Silkworth, William T. |
collection | PubMed |
description | Spindle assembly, establishment of kinetochore attachment, and sister chromatid separation must occur during mitosis in a highly coordinated fashion to ensure accurate chromosome segregation. In most vertebrate cells, the nuclear envelope must break down to allow interaction between microtubules of the mitotic spindle and the kinetochores. It was previously shown that nuclear envelope breakdown (NEB) is not coordinated with centrosome separation and that centrosome separation can be either complete at the time of NEB or can be completed after NEB. In this study, we investigated whether the timing of centrosome separation affects subsequent mitotic events such as establishment of kinetochore attachment or chromosome segregation. We used a combination of experimental and computational approaches to investigate kinetochore attachment and chromosome segregation in cells with complete versus incomplete spindle pole separation at NEB. We found that cells with incomplete spindle pole separation exhibit higher rates of kinetochore misattachments and chromosome missegregation than cells that complete centrosome separation before NEB. Moreover, our mathematical model showed that two spindle poles in close proximity do not “search” the entire cellular space, leading to formation of large numbers of syntelic attachments, which can be an intermediate stage in the formation of merotelic kinetochores. |
format | Online Article Text |
id | pubmed-3268720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-32687202012-04-16 Timing of centrosome separation is important for accurate chromosome segregation Silkworth, William T. Nardi, Isaac K. Paul, Raja Mogilner, Alex Cimini, Daniela Mol Biol Cell Articles Spindle assembly, establishment of kinetochore attachment, and sister chromatid separation must occur during mitosis in a highly coordinated fashion to ensure accurate chromosome segregation. In most vertebrate cells, the nuclear envelope must break down to allow interaction between microtubules of the mitotic spindle and the kinetochores. It was previously shown that nuclear envelope breakdown (NEB) is not coordinated with centrosome separation and that centrosome separation can be either complete at the time of NEB or can be completed after NEB. In this study, we investigated whether the timing of centrosome separation affects subsequent mitotic events such as establishment of kinetochore attachment or chromosome segregation. We used a combination of experimental and computational approaches to investigate kinetochore attachment and chromosome segregation in cells with complete versus incomplete spindle pole separation at NEB. We found that cells with incomplete spindle pole separation exhibit higher rates of kinetochore misattachments and chromosome missegregation than cells that complete centrosome separation before NEB. Moreover, our mathematical model showed that two spindle poles in close proximity do not “search” the entire cellular space, leading to formation of large numbers of syntelic attachments, which can be an intermediate stage in the formation of merotelic kinetochores. The American Society for Cell Biology 2012-02-01 /pmc/articles/PMC3268720/ /pubmed/22130796 http://dx.doi.org/10.1091/mbc.E11-02-0095 Text en © 2012 Silkworth et al. 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 (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Silkworth, William T. Nardi, Isaac K. Paul, Raja Mogilner, Alex Cimini, Daniela Timing of centrosome separation is important for accurate chromosome segregation |
title | Timing of centrosome separation is important for accurate chromosome segregation |
title_full | Timing of centrosome separation is important for accurate chromosome segregation |
title_fullStr | Timing of centrosome separation is important for accurate chromosome segregation |
title_full_unstemmed | Timing of centrosome separation is important for accurate chromosome segregation |
title_short | Timing of centrosome separation is important for accurate chromosome segregation |
title_sort | timing of centrosome separation is important for accurate chromosome segregation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268720/ https://www.ncbi.nlm.nih.gov/pubmed/22130796 http://dx.doi.org/10.1091/mbc.E11-02-0095 |
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