Faculty Opinions recommendation of Spindle assembly checkpoint of oocytes depends on a kinetochore structure determined by cohesin in meiosis I.

DNA damage acquired during meiosis can lead to infertility and miscarriage. Hence, it should be important for an oocyte to be able to detect and respond to such events in order to make a healthy egg. Here, the strategies taken by oocytes during their stages of growth to respond to DNA damaging events are reviewed. In particular, recent evidence of a novel pathway in fully grown oocytes helps prevent the formation of mature eggs with DNA damage. It has been found that fully grown germinal vesicle stage oocytes that have been DNA damaged do not arrest at this point in meiosis, but instead undergo meiotic resumption and stall during the first meiotic division. The Spindle Assembly Checkpoint, which is a well-known mitotic pathway employed by somatic cells to monitor chromosome attachment to spindle microtubules, appears to be utilised by oocytes also to respond to DNA damage. As such maturing oocytes are arrested at metaphase I due to an active Spindle Assembly Checkpoint. This is surprising given this checkpoint has been previously studied in oocytes and considered to be weak and ineffectual because of its poor ability to be activated in response to microtubule attachment errors. Therefore, the involvement of the Spindle Assembly Checkpoint in DNA damage responses of mature oocytes during meiosis I uncovers a novel second function for this ubiquitous cellular checkpoint.

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Chromosome biorientation and APC activity remain uncoupled in oocytes with reduced volume

The Journal of Cell Biology ◽

10.1083/jcb.201606134 ◽

2017 ◽

Vol 216 (12) ◽

pp. 3949-3957 ◽

Cited By ~ 13

Author(s):

Simon I.R. Lane ◽

Keith T. Jones

Keyword(s):

Cell Volume ◽

Chromosome Segregation ◽

Spindle Assembly Checkpoint ◽

Spindle Assembly ◽

Anaphase Promoting Complex ◽

Chromosome Missegregation ◽

Anaphase Onset ◽

Reduced Volume ◽

Chromosome Attachment ◽

Meiosis I

The spindle assembly checkpoint (SAC) prevents chromosome missegregation by coupling anaphase onset with correct chromosome attachment and tension to microtubules. It does this by generating a diffusible signal from free kinetochores into the cytoplasm, inhibiting the anaphase-promoting complex (APC). The volume in which this signal remains effective is unknown. This raises the possibility that cell volume may be the reason the SAC is weak, and chromosome segregation error-prone, in mammalian oocytes. Here, by a process of serial bisection, we analyzed the influence of oocyte volume on the ability of the SAC to inhibit bivalent segregation in meiosis I. We were able to generate oocytes with cytoplasmic volumes reduced by 86% and observed changes in APC activity consistent with increased SAC control. However, bivalent biorientation remained uncoupled from APC activity, leading to error-prone chromosome segregation. We conclude that volume is one factor contributing to SAC weakness in oocytes. However, additional factors likely uncouple chromosome biorientation with APC activity.

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Meiosis I inXenopusoocytes is not error-prone despite lacking spindle assembly checkpoint

Cell Cycle ◽

10.4161/cc.28562 ◽

2014 ◽

Vol 13 (10) ◽

pp. 1602-1606 ◽

Cited By ~ 5

Author(s):

Dandan Liu ◽

Hua Shao ◽

HongMei Wang ◽

X. Johné Liu

Keyword(s):

Spindle Assembly Checkpoint ◽

Spindle Assembly ◽

Meiosis I

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

The Journal of Cell Biology ◽

10.1083/jcb.201808088 ◽

2019 ◽

Vol 218 (5) ◽

pp. 1553-1563 ◽

Cited By ~ 18

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.

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Sgol2 provides a regulatory platform that coordinates essential cell cycle processes during meiosis I in oocytes

eLife ◽

10.7554/elife.01133 ◽

2013 ◽

Vol 2 ◽

Cited By ~ 38

Author(s):

Ahmed Rattani ◽

Magda Wolna ◽

Mickael Ploquin ◽

Wolfgang Helmhart ◽

Seamus Morrone ◽

...

Keyword(s):

Cell Cycle ◽

Chromosome Segregation ◽

Spindle Assembly Checkpoint ◽

Kinase Activity ◽

Spindle Assembly ◽

Fiber Formation ◽

Direct Binding ◽

Multiple Interactions ◽

Meiosis I

Accurate chromosome segregation depends on coordination between cohesion resolution and kinetochore-microtubule interactions (K-fibers), a process regulated by the spindle assembly checkpoint (SAC). How these diverse processes are coordinated remains unclear. We show that in mammalian oocytes Shugoshin-like protein 2 (Sgol2) in addition to protecting cohesin, plays an important role in turning off the SAC, in promoting the congression and bi-orientation of bivalents on meiosis I spindles, in facilitating formation of K-fibers and in limiting bivalent stretching. Sgol2’s ability to protect cohesin depends on its interaction with PP2A, as is its ability to silence the SAC, with the latter being mediated by direct binding to Mad2. In contrast, its effect on bivalent stretching and K-fiber formation is independent of PP2A and mediated by recruitment of MCAK and inhibition of Aurora C kinase activity respectively. By virtue of its multiple interactions, Sgol2 links many of the processes essential for faithful chromosome segregation.

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The spindle assembly checkpoint is not essential for CSF arrest of mouse oocytes

The Journal of Cell Biology ◽

10.1083/jcb.200405165 ◽

2004 ◽

Vol 167 (6) ◽

pp. 1037-1050 ◽

Cited By ~ 103

Author(s):

Chizuko Tsurumi ◽

Steffen Hoffmann ◽

Stephan Geley ◽

Ralph Graeser ◽

Zbigniew Polanski

Keyword(s):

Spindle Assembly Checkpoint ◽

Spindle Assembly ◽

Dominant Negative ◽

Meiotic Spindle ◽

Anaphase Promoting Complex ◽

Mouse Oocytes ◽

Cytostatic Factor ◽

C Complex ◽

Meiosis I

In Xenopus oocytes, the spindle assembly checkpoint (SAC) kinase Bub1 is required for cytostatic factor (CSF)-induced metaphase arrest in meiosis II. To investigate whether matured mouse oocytes are kept in metaphase by a SAC-mediated inhibition of the anaphase-promoting complex/cyclosome (APC/C) complex, we injected a dominant-negative Bub1 mutant (Bub1dn) into mouse oocytes undergoing meiosis in vitro. Passage through meiosis I was accelerated, but even though the SAC was disrupted, injected oocytes still arrested at metaphase II. Bub1dn-injected oocytes released from CSF and treated with nocodazole to disrupt the second meiotic spindle proceeded into interphase, whereas noninjected control oocytes remained arrested at metaphase. Similar results were obtained using dominant-negative forms of Mad2 and BubR1, as well as checkpoint resistant dominant APC/C activating forms of Cdc20. Thus, SAC proteins are required for checkpoint functions in meiosis I and II, but, in contrast to frog eggs, the SAC is not required for establishing or maintaining the CSF arrest in mouse oocytes.

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Loss of centromeric RNA activates the spindle assembly checkpoint in mammalian female meiosis I

The Journal of Cell Biology ◽

10.1083/jcb.202011153 ◽

2021 ◽

Vol 220 (10) ◽

Author(s):

Tianyu Wu ◽

Simon I.R. Lane ◽

Stephanie L. Morgan ◽

Feng Tang ◽

Keith T. Jones

Keyword(s):

Spindle Assembly Checkpoint ◽

Structural Integrity ◽

Repetitive Sequences ◽

Spindle Assembly ◽

Structural Basis ◽

Female Meiosis ◽

Satellite Repeats ◽

Minor Satellite ◽

Mammalian Female ◽

Meiosis I

The repetitive sequences of DNA centromeric regions form the structural basis for kinetochore assembly. Recently they were found to be transcriptionally active in mitosis, with their RNAs providing noncoding functions. Here we explore the role, in mouse oocytes, of transcripts generated from within the minor satellite repeats. Depletion of minor satellite transcripts delayed progression through meiosis I by activation of the spindle assembly checkpoint. Arrested oocytes had poorly congressed chromosomes, and centromeres were frequently split by microtubules. Thus, we have demonstrated that the centromeric RNA plays a specific role in female meiosis I compared with mitosis and is required for maintaining the structural integrity of centromeres. This may contribute to the high aneuploidy rates observed in female meiosis.

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