Delayed APC/C activation extends the first mitosis of mouse embryos.
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Date
2017-08-29ICR Author
Author
Ajduk, A
Strauss, B
Pines, J
Zernicka-Goetz, M
Type
Journal Article
Metadata
Show full item recordAbstract
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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Subject
Animals
Mice
Mitosis
Gene Expression
Gene Expression Regulation, Developmental
Embryonic Development
Genes, Reporter
Transcriptional Activation
Cyclin B1
Cyclin A2
Proteolysis
M Phase Cell Cycle Checkpoints
Anaphase-Promoting Complex-Cyclosome
Biomarkers
Language
eng
Date accepted
2017-06-29
License start date
2017-08-29
Citation
Scientific reports, 2017, 7 (1), pp. 9682 - ?
Publisher
Springer Science and Business Media LLC