Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1783260010660233216 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5575289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT ajdukanna delayedapccactivationextendsthefirstmitosisofmouseembryos AT straussbernhard delayedapccactivationextendsthefirstmitosisofmouseembryos AT pinesjonathon delayedapccactivationextendsthefirstmitosisofmouseembryos AT zernickagoetzmagdalena delayedapccactivationextendsthefirstmitosisofmouseembryos |