The spindle checkpoint, APC/CCdc20, and APC/CCdh1 play distinct roles in connecting mitosis to S phase
العنوان: | The spindle checkpoint, APC/CCdc20, and APC/CCdh1 play distinct roles in connecting mitosis to S phase |
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المؤلفون: | Janneke Ogink, Rob M. F. Wolthuis, Linda Clijsters |
المصدر: | The Journal of Cell Biology |
بيانات النشر: | Rockefeller University Press, 2013. |
سنة النشر: | 2013 |
مصطلحات موضوعية: | Cell cycle checkpoint, Cdc20 Proteins, Cyclin B, Mitosis, Cell Cycle Proteins, Article, Anaphase-Promoting Complex-Cyclosome, S Phase, Antigens, CD, Cell Line, Tumor, Humans, Cyclin B1, Biochemical switches in the cell cycle, Research Articles, biology, Kinetochore, Geminin, Nuclear Proteins, Ubiquitin-Protein Ligase Complexes, Cell Biology, G2-M DNA damage checkpoint, Cadherins, Cell biology, Spindle checkpoint, Mitotic exit, embryonic structures, biology.protein, M Phase Cell Cycle Checkpoints, Anaphase-promoting complex |
الوصف: | The spindle checkpoint, APC/C-Cdc20, and APC/C-Cdh1 act successively to connect disappearance of geminin and cyclin B1 to a peak of Cdt1 and Cdc6. DNA replication depends on a preceding licensing event by Cdt1 and Cdc6. In animal cells, relicensing after S phase but before mitosis is prevented by the Cdt1 inhibitor geminin and mitotic cyclin activity. Here, we show that geminin, like cyclin B1 and securin, is a bona fide target of the spindle checkpoint and APC/CCdc20. Cyclin B1 and geminin are degraded simultaneously during metaphase, which directs Cdt1 accumulation on segregating sister chromatids. Subsequent activation of APC/CCdh1 leads to degradation of Cdc6 well before Cdt1 becomes unstable in a replication-coupled manner. In mitosis, the spindle checkpoint supports Cdt1 accumulation, which promotes S phase onset. We conclude that the spindle checkpoint, APC/CCdc20, and APC/CCdh1 act successively to ensure that the disappearance of licensing inhibitors coincides exactly with a peak of Cdt1 and Cdc6. Whereas cell cycle entry from quiescence requires Cdc6 resynthesis, our results indicate that proliferating cells use a window of time in mitosis, before Cdc6 is degraded, as an earlier opportunity to direct S phase. |
تدمد: | 1540-8140 0021-9525 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c9aebdaea5f201df900a9f7fe5ce9dc2 https://doi.org/10.1083/jcb.201211019 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....c9aebdaea5f201df900a9f7fe5ce9dc2 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15408140 00219525 |
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