Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Silkworth, William T., Nardi, Isaac K., Paul, Raja, Mogilner, Alex, Cimini, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
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
_version_ 1782222407205912576
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
work_keys_str_mv AT silkworthwilliamt timingofcentrosomeseparationisimportantforaccuratechromosomesegregation
AT nardiisaack timingofcentrosomeseparationisimportantforaccuratechromosomesegregation
AT paulraja timingofcentrosomeseparationisimportantforaccuratechromosomesegregation
AT mogilneralex timingofcentrosomeseparationisimportantforaccuratechromosomesegregation
AT ciminidaniela timingofcentrosomeseparationisimportantforaccuratechromosomesegregation