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The association of Plk1 with the astrin–kinastrin complex promotes formation and maintenance of a metaphase plate

Errors in mitotic chromosome segregation can lead to DNA damage and aneuploidy, both hallmarks of cancer. To achieve synchronous error-free segregation, mitotic chromosomes must align at the metaphase plate with stable amphitelic attachments to microtubules emanating from opposing spindle poles. The...

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Autores principales: Geraghty, Zoë, Barnard, Christina, Uluocak, Pelin, Gruneberg, Ulrike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803464/
https://www.ncbi.nlm.nih.gov/pubmed/33288550
http://dx.doi.org/10.1242/jcs.251025
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author Geraghty, Zoë
Barnard, Christina
Uluocak, Pelin
Gruneberg, Ulrike
author_facet Geraghty, Zoë
Barnard, Christina
Uluocak, Pelin
Gruneberg, Ulrike
author_sort Geraghty, Zoë
collection PubMed
description Errors in mitotic chromosome segregation can lead to DNA damage and aneuploidy, both hallmarks of cancer. To achieve synchronous error-free segregation, mitotic chromosomes must align at the metaphase plate with stable amphitelic attachments to microtubules emanating from opposing spindle poles. The astrin–kinastrin (astrin is also known as SPAG5 and kinastrin as SKAP) complex, also containing DYNLL1 and MYCBP, is a spindle and kinetochore protein complex with important roles in bipolar spindle formation, chromosome alignment and microtubule–kinetochore attachment. However, the molecular mechanisms by which astrin–kinastrin fulfils these diverse roles are not fully understood. Here, we characterise a direct interaction between astrin and the mitotic kinase Plk1. We identify the Plk1-binding site on astrin as well as four Plk1 phosphorylation sites on astrin. Regulation of astrin by Plk1 is dispensable for bipolar spindle formation and bulk chromosome congression, but promotes stable microtubule–kinetochore attachments and metaphase plate maintenance. It is known that Plk1 activity is required for effective microtubule–kinetochore attachment formation, and we suggest that astrin phosphorylation by Plk1 contributes to this process.
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spelling pubmed-78034642021-01-22 The association of Plk1 with the astrin–kinastrin complex promotes formation and maintenance of a metaphase plate Geraghty, Zoë Barnard, Christina Uluocak, Pelin Gruneberg, Ulrike J Cell Sci Short Report Errors in mitotic chromosome segregation can lead to DNA damage and aneuploidy, both hallmarks of cancer. To achieve synchronous error-free segregation, mitotic chromosomes must align at the metaphase plate with stable amphitelic attachments to microtubules emanating from opposing spindle poles. The astrin–kinastrin (astrin is also known as SPAG5 and kinastrin as SKAP) complex, also containing DYNLL1 and MYCBP, is a spindle and kinetochore protein complex with important roles in bipolar spindle formation, chromosome alignment and microtubule–kinetochore attachment. However, the molecular mechanisms by which astrin–kinastrin fulfils these diverse roles are not fully understood. Here, we characterise a direct interaction between astrin and the mitotic kinase Plk1. We identify the Plk1-binding site on astrin as well as four Plk1 phosphorylation sites on astrin. Regulation of astrin by Plk1 is dispensable for bipolar spindle formation and bulk chromosome congression, but promotes stable microtubule–kinetochore attachments and metaphase plate maintenance. It is known that Plk1 activity is required for effective microtubule–kinetochore attachment formation, and we suggest that astrin phosphorylation by Plk1 contributes to this process. The Company of Biologists Ltd 2021-01-08 /pmc/articles/PMC7803464/ /pubmed/33288550 http://dx.doi.org/10.1242/jcs.251025 Text en © 2021. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Short Report
Geraghty, Zoë
Barnard, Christina
Uluocak, Pelin
Gruneberg, Ulrike
The association of Plk1 with the astrin–kinastrin complex promotes formation and maintenance of a metaphase plate
title The association of Plk1 with the astrin–kinastrin complex promotes formation and maintenance of a metaphase plate
title_full The association of Plk1 with the astrin–kinastrin complex promotes formation and maintenance of a metaphase plate
title_fullStr The association of Plk1 with the astrin–kinastrin complex promotes formation and maintenance of a metaphase plate
title_full_unstemmed The association of Plk1 with the astrin–kinastrin complex promotes formation and maintenance of a metaphase plate
title_short The association of Plk1 with the astrin–kinastrin complex promotes formation and maintenance of a metaphase plate
title_sort association of plk1 with the astrin–kinastrin complex promotes formation and maintenance of a metaphase plate
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803464/
https://www.ncbi.nlm.nih.gov/pubmed/33288550
http://dx.doi.org/10.1242/jcs.251025
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