After fertilization, remodeling of the oocyte and sperm genomes is essential to convert these highly differentiated and transcriptionally quiescent cells into early cleavage-stage blastomeres that are transcriptionally active and totipotent. This developmental transition is accompanied by cell cycle adaptation, such as lengthening or shortening of the gap phases G1 and G2. However, regulation of these cell cycle changes is poorly understood, especially in mammals. Checkpoint kinase 1 (CHK1) is a protein kinase that regulates cell cycle progression in somatic cells. Here, we show that CHK1 regulates cell cycle progression in early mouse embryos by restraining CDK1 kinase activity due to CDC25A phosphatase degradation. CHK1 kinase also ensures the long G2 phase needed for genome activation and reprogramming gene expression in two-cell stage mouse embryos. Finally, Chk1 depletion leads to DNA damage and chromosome segregation errors that result in aneuploidy and infertility.

• Keywords
• CDC25A phosphatase, CDK1 kinase, CHK1 kinase, cell cycle regulation, early mouse embryos,
• Publication type
• Journal Article MeSH

Cells are equipped with a diverse network of signaling and regulatory proteins that function as cell cycle regulators and checkpoint proteins to ensure the proper progression of cell division. A key regulator of cell division is polo-like kinase 1 (PLK1), a member of the serine/threonine kinase family that plays an important role in regulating the mitotic and meiotic cell cycle. The phosphorylation of specific substrates mediated by PLK1 controls nuclear envelope breakdown (NEBD), centrosome maturation, proper spindle assembly, chromosome segregation, and cytokinesis. In mammalian oogenesis, PLK1 is essential for resuming meiosis before ovulation and for establishing the meiotic spindle. Among other potential roles, PLK1 regulates the localized translation of spindle-enriched mRNAs by phosphorylating and thereby inhibiting the translational repressor 4E-BP1, a downstream target of the mTOR (mammalian target of rapamycin) pathway. In this review, we summarize the functions of PLK1 in mitosis, meiosis, and cytokinesis and focus on the role of PLK1 in regulating mRNA translation. However, knowledge of the role of PLK1 in the regulation of meiosis remains limited.

• Keywords
• PLK1, mRNA translation, meiosis, mitosis, oocytes, polo-like kinase 1, spindle,
• MeSH
• Humans MeSH
• Meiosis MeSH
• Mitosis MeSH
• Polo-Like Kinase 1 MeSH
• Protein Serine-Threonine Kinases * metabolism   MeSH
• Cell Cycle Proteins * metabolism   MeSH
• Proto-Oncogene Proteins metabolism   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Protein Serine-Threonine Kinases * MeSH
• Cell Cycle Proteins * MeSH
• Proto-Oncogene Proteins MeSH

The Aurora protein kinases are well-established regulators of spindle building and chromosome segregation in mitotic and meiotic cells. In mouse oocytes, there is significant Aurora kinase A (AURKA) compensatory abilities when the other Aurora kinase homologs are deleted. Whether the other homologs, AURKB or AURKC can compensate for loss of AURKA is not known. Using a conditional mouse oocyte knockout model, we demonstrate that this compensation is not reciprocal because female oocyte-specific knockout mice are sterile, and their oocytes fail to complete meiosis I. In determining AURKA-specific functions, we demonstrate that its first meiotic requirement is to activate Polo-like kinase 1 at acentriolar microtubule organizing centers (aMTOCs; meiotic spindle poles). This activation induces fragmentation of the aMTOCs, a step essential for building a bipolar spindle. We also show that AURKA is required for regulating localization of TACC3, another protein required for spindle building. We conclude that AURKA has multiple functions essential to completing MI that are distinct from AURKB and AURKC.

• MeSH
• Spindle Apparatus genetics   MeSH
• Aurora Kinase A genetics   MeSH
• Aurora Kinase B genetics   MeSH
• Aurora Kinase C genetics   MeSH
• Cell Nucleus Division genetics   MeSH
• Fetal Proteins genetics   MeSH
• Humans MeSH
• Meiosis genetics   MeSH
• Mice MeSH
• Oocytes growth & development   metabolism   MeSH
• Microtubule-Organizing Center metabolism   MeSH
• Polo-Like Kinase 1 MeSH
• Spindle Poles genetics   MeSH
• Protein Serine-Threonine Kinases genetics   MeSH
• Microtubule-Associated Proteins genetics   MeSH
• Cell Cycle Proteins genetics   MeSH
• Proto-Oncogene Proteins genetics   MeSH
• Chromosome Segregation genetics   MeSH
• Gene Expression Regulation, Developmental genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Aurkb protein, mouse MeSH Browser
• Aurkc protein, mouse MeSH Browser
• Aurora Kinase A MeSH
• Aurora Kinase B MeSH
• Aurora Kinase C MeSH
• Fetal Proteins MeSH
• Protein Serine-Threonine Kinases MeSH
• Microtubule-Associated Proteins MeSH
• Cell Cycle Proteins MeSH
• Proto-Oncogene Proteins MeSH
• TACC3 protein, mouse MeSH Browser

The degradation of maternally provided molecules is a very important process during early embryogenesis. However, the vast majority of studies deals with mRNA degradation and protein degradation is only a very little explored process yet. The aim of this article was to summarize current knowledge about the protein degradation during embryogenesis of mammals. In addition to resuming of known data concerning mammalian embryogenesis, we tried to fill the gaps in knowledge by comparison with facts known about protein degradation in early embryos of non-mammalian species. Maternal protein degradation seems to be driven by very strict rules in terms of specificity and timing. The degradation of some maternal proteins is certainly necessary for the normal course of embryonic genome activation (EGA) and several concrete proteins that need to be degraded before major EGA have been already found. Nevertheless, the most important period seems to take place even before preimplantation development-during oocyte maturation. The defects arisen during this period seems to be later irreparable.

• Keywords
• Autophagy, Embryonic genome activation, Maternal to zygotic transition, Proteasome system, Ubiquitin, Ubiquitin ligase,
• MeSH
• Embryo, Nonmammalian metabolism   physiology   MeSH
• Embryo, Mammalian metabolism   physiology   MeSH
• Embryonic Development physiology   MeSH
• Genome physiology   MeSH
• Humans MeSH
• Oocytes metabolism   physiology   MeSH
• Proteins metabolism   MeSH
• Gene Expression Regulation, Developmental physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Proteins MeSH

Homologous chromosome segregation during meiosis I (MI) in mammalian oocytes is carried out by the acentrosomal MI spindles. Whereas studies in human oocytes identified Ran GTPase as a crucial regulator of the MI spindle function, experiments in mouse oocytes questioned the generality of this notion. Here, we use live-cell imaging with fluorescent probes and Förster resonance energy transfer (FRET) biosensors to monitor the changes in Ran and importin β signaling induced by perturbations of Ran in mouse oocytes while examining the MI spindle dynamics. We show that unlike RanT24N employed in previous studies, a RanT24N, T42A double mutant inhibits RanGEF without perturbing cargo binding to importin β and disrupts MI spindle function in chromosome segregation. Roles of Ran and importin β in the coalescence of microtubule organizing centers (MTOCs) and MI spindle assembly are further supported by the use of the chemical inhibitor importazole, whose effects are partially rescued by the GTP hydrolysis-resistant RanQ69L mutant. These results indicate that RanGTP is essential for MI spindle assembly and function both in humans and mice.

• Keywords
• RanGTP, importazole, importin β, meiosis I, oocyte,
• MeSH
• Spindle Apparatus physiology   MeSH
• beta Karyopherins genetics   metabolism   MeSH
• Nuclear Proteins genetics   metabolism   MeSH
• Meiosis physiology   MeSH
• Microtubules metabolism   MeSH
• Mutation MeSH
• Mice MeSH
• Oocytes cytology   metabolism   MeSH
• Cell Cycle Proteins genetics   metabolism   MeSH
• ran GTP-Binding Protein genetics   metabolism   MeSH
• Chromosome Segregation MeSH
• Guanine Nucleotide Exchange Factors genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• beta Karyopherins MeSH
• Nuclear Proteins MeSH
• Cell Cycle Proteins MeSH
• ran GTP-Binding Protein MeSH
• Rcc1 protein, mouse MeSH Browser
• Guanine Nucleotide Exchange Factors MeSH

BACKGROUND: SIRT1 histone deacetylase acts on many epigenetic and non-epigenetic targets. It is thought that SIRT1 is involved in oocyte maturation; therefore, the importance of the ooplasmic SIRT1 pool for the further fate of mature oocytes has been strongly suggested. We hypothesised that SIRT1 plays the role of a signalling molecule in mature oocytes through selected epigenetic and non-epigenetic regulation. RESULTS: We observed SIRT1 re-localisation in mature oocytes and its association with spindle microtubules. In mature oocytes, SIRT1 distribution shows a spindle-like pattern, and spindle-specific SIRT1 action decreases α-tubulin acetylation. Based on the observation of the histone code in immature and mature oocytes, we suggest that SIRT1 is mostly predestined for an epigenetic mode of action in the germinal vesicles (GVs) of immature oocytes. Accordingly, BML-278-driven trimethylation of lysine K9 in histone H3 in mature oocytes is considered to be a result of GV epigenetic transformation. CONCLUSIONS: Taken together, our observations point out the dual spatiotemporal SIRT1 action in oocytes, which can be readily switched from the epigenetic to non-epigenetic mode of action depending on the progress of meiosis.

• Keywords
• Epigenetics, Histone code, In vitro maturation, Oocyte, SIRT1, Sirtuin 1,
• Publication type
• Journal Article MeSH