Checkpoint control of the G2/M phase transition during the first mitotic cycle in mammalian eggs
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The high incidence of chromosomally abnormal human embryos is frequently assumed to be due to a lack of checkpoint controls operating during early embryogenesis. In our study we have analysed when these mechanisms first become functional. Mouse oocytes treated in late metaphase I with either of two different cyclin-dependent kinase inhibitors [butyrolactone 1 (BL1) or 6-dimethylaminopurine (6-DMAP)] form nuclei in the cytoplasm. BL1-treated eggs enter S-phase at 16-18 h post-treatment and, after completion of DNA synthesis, cleave to 2-cell stage embryos. 6-DMAP treatment results in the rapid initiation of DNA synthesis, its completion by 12 h and then arrest in the G2 phase. Thus, two different cell cycle stages can be obtained at the same time point after the initiation of treatment: G1- after BL1 and G2-staged nuclei after 6-DMAP treatment. That this approach greatly facilitates cell cycle studies has been shown by analysing checkpoint function during the first division. Whilst G2-staged eggs enter M phase within 2-3 h when 6-DMAP is washed out, the onset of M phase is delayed after their fusion to G1 (BL1) cells. Here M phase occurs only after the less advanced nucleus completes DNA replication. Our results indicate that checkpoints in mammalian eggs are functional during the first mitotic cycle.
- MeSH
- adenin analogy a deriváty farmakologie MeSH
- cyklin-dependentní kinasy antagonisté a inhibitory MeSH
- DNA biosyntéza MeSH
- G1 fáze MeSH
- G2 fáze * MeSH
- gama-butyrolakton analogy a deriváty farmakologie MeSH
- inhibitory enzymů farmakologie MeSH
- mitóza * MeSH
- myši inbrední C57BL MeSH
- myši inbrední CBA MeSH
- myši MeSH
- oocyty cytologie metabolismus MeSH
- zvířata MeSH
- zygota MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- adenin MeSH
- butyrolactone I MeSH Prohlížeč
- cyklin-dependentní kinasy MeSH
- DNA MeSH
- gama-butyrolakton MeSH
- inhibitory enzymů MeSH
- N(6),N(6)-dimethyladenine MeSH Prohlížeč