Spindle assembly checkpoint regulation of chromosome segregation in mammalian oocytes

2013 ◽  
Vol 25 (3) ◽  
pp. 472 ◽  
Author(s):  
Zbigniew Polanski
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Cell Cycle Control ◽  
Genetic Material ◽  
Spindle Assembly ◽  
Female Meiosis ◽  
Mammalian Oocyte ◽  
Oocyte Meiosis ◽  
Surveillance Mechanism

The spindle assembly checkpoint (SAC) is a surveillance mechanism that monitors the quality of the spindle during division and blocks anaphase entry in the presence of anomalies that could result in erroneous segregation of the chromosomes. Because human aneuploidy is mainly linked to the erroneous segregation of genetic material in oocytes, the issue of the effectiveness of the SAC in female meiosis is especially important. The present review summarises our understanding of the SAC control of mammalian oocyte meiosis, including its possible impact on the incidence of embryonic aneuploidy. Owing to the peculiarities of cell cycle control in female meiosis, the integration of the SAC within such a specific environment results in several unusual situations, which are also discussed.

Evidence that the spindle assembly checkpoint does not regulate APCFzy activity in Drosophila female meiosis

Genome ◽  
2012 ◽  
Vol 55 (1) ◽  
pp. 63-67 ◽  
Author(s):  
Osamah Batiha ◽  
Andrew Swan
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Cyclin B ◽  
Meiotic Spindle ◽  
Loss Of Function ◽  
Female Meiosis ◽  
Chromosome Attachment ◽  
Spindle Microtubules ◽  
Made In

The spindle assembly checkpoint (SAC) plays an important role in mitotic cells to sense improper chromosome attachment to spindle microtubules and to inhibit APCFzy-dependent destruction of cyclin B and Securin; consequent initiation of anaphase until correct attachments are made. In Drosophila , SAC genes have been found to play a role in ensuring proper chromosome segregation in meiosis, possibly reflecting a similar role for the SAC in APCFzy inhibition during meiosis. We found that loss of function mutations in SAC genes, Mad2, zwilch, and mps1, do not lead to the predicted rise in APCFzy-dependent degradation of cyclin B either globally throughout the egg or locally on the meiotic spindle. Further, the SAC is not responsible for the inability of APCFzy to target cyclin B and promote anaphase in metaphase II arrested eggs from cort mutant females. Our findings support the argument that SAC proteins play checkpoint independent roles in Drosophila female meiosis and that other mechanisms must function to control APC activity.

scholarly journals Recent Progress on the Localization of the Spindle Assembly Checkpoint Machinery to Kinetochores

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 278 ◽  
Author(s):  
Zhen Dou ◽  
Diogjena Prifti ◽  
Ping Gui ◽  
Xing Liu ◽  
Sabine Elowe ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Genome Stability ◽  
Cell Cycle Progression ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Progression ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Microtubule Attachment ◽  
Surveillance Mechanism

Faithful chromosome segregation during mitosis is crucial for maintaining genome stability. The spindle assembly checkpoint (SAC) is a surveillance mechanism that ensures accurate mitotic progression. Defective SAC signaling leads to premature sister chromatid separation and aneuploid daughter cells. Mechanistically, the SAC couples the kinetochore microtubule attachment status to the cell cycle progression machinery. In the presence of abnormal kinetochore microtubule attachments, the SAC prevents the metaphase-to-anaphase transition through a complex kinase-phosphatase signaling cascade which results in the correct balance of SAC components recruited to the kinetochore. The correct kinetochore localization of SAC proteins is a prerequisite for robust SAC signaling and, hence, accurate chromosome segregation. Here, we review recent progresses on the kinetochore recruitment of core SAC factors.

scholarly journals Cyclin B3 is required for metaphase to anaphase transition in oocyte meiosis I

2019 ◽  
Vol 218 (5) ◽  
pp. 1553-1563 ◽  
Author(s):  
Yufei Li ◽  
Leyun Wang ◽  
Linlin Zhang ◽  
Zhengquan He ◽  
Guihai Feng ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Cell Cycle Control ◽  
Spindle Assembly ◽  
Specific Cell ◽  
Anaphase Promoting Complex ◽  
Cyclin Dependent Kinases ◽  
Oocyte Meiosis ◽  
Cyclin B3 ◽  
Meiosis I

Meiosis with a single round of DNA replication and two successive rounds of chromosome segregation requires specific cyclins associated with cyclin-dependent kinases (CDKs) to ensure its fidelity. But how cyclins control the distinctive meiosis is still largely unknown. In this study, we explored the role of cyclin B3 in female meiosis by generating Ccnb3 mutant mice via CRISPR/Cas9. Ccnb3 mutant oocytes characteristically arrested at metaphase I (MetI) with normal spindle assembly and lacked enough anaphase-promoting complex/cyclosome (APC/C) activity, which is spindle assembly checkpoint (SAC) independent, to initiate anaphase I (AnaI). Securin siRNA or CDK1 inhibitor supplements rescued the MetI arrest. Furthermore, CCNB3 directly interacts with CDK1 to exert kinase function. Besides, the MetI arrest oocytes had normal development after intracytoplasmic sperm injection (ICSI) or parthenogenetic activation (PA), along with releasing the sister chromatids, which implies that Ccnb3 exclusively functioned in meiosis I, rather than meiosis II. Our study sheds light on the specific cell cycle control of cyclins in meiosis.

scholarly journals WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Changyin Zhou ◽  
Yilong Miao ◽  
Xue Zhang ◽  
Bo Xiong
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Polar Body ◽  
Spindle Assembly ◽  
Protein Levels ◽  
Meiotic Progression ◽  
Oocyte Meiosis ◽  
Chromosome Alignment ◽  
Porcine Oocyte ◽  
Polar Body Extrusion

Abstract Background In mitotic cells, WAPL acts as a cohesin release factor to remove cohesin complexes from chromosome arms during prophase to allow the accurate chromosome segregation in anaphase. However, we have recently documented that Wapl exerts a unique meiotic function in the spindle assembly checkpoint (SAC) control through maintaining Bub3 stability during mouse oocyte meiosis I. Whether this noncanonical function is conserved among species is still unknown. Methods We applied RNAi-based gene silencing approach to deplete WAPL in porcine oocytes, validating the conserved roles of WAPL in the regulation of SAC activity during mammalian oocyte maturation. We also employed immunostaining, immunoblotting and image quantification analyses to test the WAPL depletion on the meiotic progression, spindle assembly, chromosome alignment and dynamics of SAC protein in porcine oocytes. Results We showed that depletion of WAPL resulted in the accelerated meiotic progression by displaying the precocious polar body extrusion and compromised spindle assembly and chromosome alignment. Notably, we observed that the protein level of BUB3 was substantially reduced in WAPL-depleted oocytes, especially at kinetochores. Conclusions Collectively, our data demonstrate that WAPL participates in the porcine oocyte meiotic progression through maintenance of BUB3 protein levels and SAC activity. This meiotic function of WAPL in oocytes is highly conserved between pigs and mice.

scholarly journals CENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dalileh Nabi ◽  
Hauke Drechsler ◽  
Johannes Pschirer ◽  
Franz Korn ◽  
Nadine Schuler ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Polar Body ◽  
Spindle Assembly ◽  
V Protein ◽  
Oocyte Meiosis ◽  
Spindle Microtubules ◽  
Polar Body Extrusion ◽  
Metaphase I

AbstractProper chromosome segregation is essential to avoid aneuploidy, yet this process fails with increasing age in mammalian oocytes. Here we report a role for the scarcely described protein CENP-V in oocyte spindle formation and chromosome segregation. We show that depending on the oocyte maturation state, CENP-V localizes to centromeres, to microtubule organizing centers, and to spindle microtubules. We find that Cenp-V−/− oocytes feature severe deficiencies, including metaphase I arrest, strongly reduced polar body extrusion, increased numbers of mis-aligned chromosomes and aneuploidy, multipolar spindles, unfocused spindle poles and loss of kinetochore spindle fibres. We also show that CENP-V protein binds, diffuses along, and bundles microtubules in vitro. The spindle assembly checkpoint arrests about half of metaphase I Cenp-V−/− oocytes from young adults only. This finding suggests checkpoint weakening in ageing oocytes, which mature despite carrying mis-aligned chromosomes. Thus, CENP-V is a microtubule bundling protein crucial to faithful oocyte meiosis, and Cenp-V−/− oocytes reveal age-dependent weakening of the spindle assembly checkpoint.

scholarly journals Xenopus oocyte meiosis lacks spindle assembly checkpoint control

2013 ◽  
Vol 201 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Hua Shao ◽  
Ruizhen Li ◽  
Chunqi Ma ◽  
Eric Chen ◽  
X. Johné Liu
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Xenopus Laevis Oocytes ◽  
Checkpoint Control ◽  
Oocyte Meiosis ◽  
Complete Disruption ◽  
Spindle Microtubules ◽  
Surveillance Mechanism ◽  
Mammalian Eggs ◽  
Mitosis And Meiosis

The spindle assembly checkpoint (SAC) functions as a surveillance mechanism to detect chromosome misalignment and to delay anaphase until the errors are corrected. The SAC is thought to control mitosis and meiosis, including meiosis in mammalian eggs. However, it remains unknown if meiosis in the eggs of nonmammalian vertebrate species is also regulated by SAC. Using a novel karyotyping technique, we demonstrate that complete disruption of spindle microtubules in Xenopus laevis oocytes did not affect the bivalent-to-dyad transition at the time oocytes are undergoing anaphase I. These oocytes also acquired the ability to respond to parthenogenetic activation, which indicates proper metaphase II arrest. Similarly, oocytes exhibiting monopolar spindles, via inhibition of aurora B or Eg5 kinesin, underwent monopolar anaphase on time and without additional intervention. Therefore, the metaphase-to-anaphase transition in frog oocytes is not regulated by SAC.

scholarly journals Monitoring the fidelity of mitotic chromosome segregation by the spindle assembly checkpoint

2011 ◽  
Vol 44 (5) ◽  
pp. 391-400 ◽  
Author(s):  
P. Silva ◽  
J. Barbosa ◽  
A. V. Nascimento ◽  
J. Faria ◽  
R. Reis ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Chromosome ◽  
Spindle Assembly
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