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Delayed APC/C activation extends the first mitosis of mouse embryos

The correct temporal regulation of mitosis underpins genomic stability because it ensures the alignment of chromosomes on the mitotic spindle that is required for their proper segregation to the two daughter cells. Crucially, sister chromatid separation must be delayed until all the chromosomes have...

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Autores principales: Ajduk, Anna, Strauss, Bernhard, Pines, Jonathon, Zernicka-Goetz, Magdalena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575289/
https://www.ncbi.nlm.nih.gov/pubmed/28851945
http://dx.doi.org/10.1038/s41598-017-09526-1
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author Ajduk, Anna
Strauss, Bernhard
Pines, Jonathon
Zernicka-Goetz, Magdalena
author_facet Ajduk, Anna
Strauss, Bernhard
Pines, Jonathon
Zernicka-Goetz, Magdalena
author_sort Ajduk, Anna
collection PubMed
description The correct temporal regulation of mitosis underpins genomic stability because it ensures the alignment of chromosomes on the mitotic spindle that is required for their proper segregation to the two daughter cells. Crucially, sister chromatid separation must be delayed until all the chromosomes have attached to the spindle; this is achieved by the Spindle Assembly Checkpoint (SAC) that inhibits the Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase. In many species the first embryonic M-phase is significantly prolonged compared to the subsequent divisions, but the reason behind this has remained unclear. Here, we show that the first M-phase in the mouse embryo is significantly extended due to a delay in APC/C activation. Unlike in somatic cells, where the APC/C first targets cyclin A2 for degradation at nuclear envelope breakdown (NEBD), we find that in zygotes cyclin A2 remains stable for a significant period of time after NEBD. Our findings that the SAC prevents cyclin A2 degradation, whereas over-expressed Plk1 stimulates it, support our conclusion that the delay in cyclin A2 degradation is caused by low APC/C activity. As a consequence of delayed APC/C activation cyclin B1 stability in the first mitosis is also prolonged, leading to the unusual length of the first M-phase.
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spelling pubmed-55752892017-09-01 Delayed APC/C activation extends the first mitosis of mouse embryos Ajduk, Anna Strauss, Bernhard Pines, Jonathon Zernicka-Goetz, Magdalena Sci Rep Article The correct temporal regulation of mitosis underpins genomic stability because it ensures the alignment of chromosomes on the mitotic spindle that is required for their proper segregation to the two daughter cells. Crucially, sister chromatid separation must be delayed until all the chromosomes have attached to the spindle; this is achieved by the Spindle Assembly Checkpoint (SAC) that inhibits the Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase. In many species the first embryonic M-phase is significantly prolonged compared to the subsequent divisions, but the reason behind this has remained unclear. Here, we show that the first M-phase in the mouse embryo is significantly extended due to a delay in APC/C activation. Unlike in somatic cells, where the APC/C first targets cyclin A2 for degradation at nuclear envelope breakdown (NEBD), we find that in zygotes cyclin A2 remains stable for a significant period of time after NEBD. Our findings that the SAC prevents cyclin A2 degradation, whereas over-expressed Plk1 stimulates it, support our conclusion that the delay in cyclin A2 degradation is caused by low APC/C activity. As a consequence of delayed APC/C activation cyclin B1 stability in the first mitosis is also prolonged, leading to the unusual length of the first M-phase. Nature Publishing Group UK 2017-08-29 /pmc/articles/PMC5575289/ /pubmed/28851945 http://dx.doi.org/10.1038/s41598-017-09526-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ajduk, Anna
Strauss, Bernhard
Pines, Jonathon
Zernicka-Goetz, Magdalena
Delayed APC/C activation extends the first mitosis of mouse embryos
title Delayed APC/C activation extends the first mitosis of mouse embryos
title_full Delayed APC/C activation extends the first mitosis of mouse embryos
title_fullStr Delayed APC/C activation extends the first mitosis of mouse embryos
title_full_unstemmed Delayed APC/C activation extends the first mitosis of mouse embryos
title_short Delayed APC/C activation extends the first mitosis of mouse embryos
title_sort delayed apc/c activation extends the first mitosis of mouse embryos
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575289/
https://www.ncbi.nlm.nih.gov/pubmed/28851945
http://dx.doi.org/10.1038/s41598-017-09526-1
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