Cyclin A2 modulates kinetochore–microtubule attachment in meiosis II

Zhang, Qinghua; Yuen, Wai Shan; Adhikari, Deepak; Flegg, Jennifer A.; FitzHarris, Greg; Conti, Marco; Siciński, Piotr; Nabti, Ibtissem; Marangos, Petros; Carroll, John

doi:10.1083/jcb.201607111

Cited by 31 publications

(37 citation statements)

References 69 publications

(90 reference statements)

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“…This is more than previously reported (about 5% of attachments were scored as merotelic or lateral in MII oocytes by [Ref. ]). The discrepancy between our result and those reported by [Ref.…”

Section: Resultsmentioning

confidence: 52%

“…], where cells undergo cold treatment to remove less stable microtubules that are not attached to the kinetochores in a stabilizing buffer instead of PBS as used by [Ref. ], to preserve MTs. In addition, we acquired the images with a microscope equipped with an Airyscan microscope module (Zeiss) to achieve super‐resolution, allowing improved identification of thin MTs.…”

Section: Resultsmentioning

confidence: 99%

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Post‐metaphase correction of aberrant kinetochore‐microtubule attachments in mammalian eggs

et al. 2019

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The accuracy of the two sequential meiotic divisions in oocytes is essential for creating a haploid gamete with a normal chromosomal content. Here, we have analysed the 3D dynamics of chromosomes during the second meiotic division in live mouse oocytes. We find that chromosomes form stable kinetochore–microtubule attachments at the end of prometaphase II stage that are retained until anaphase II onset. Remarkably, we observe that more than 20% of the kinetochore–microtubule attachments at the metaphase II stage are merotelic or lateral. However, < 1% of all chromosomes at onset of anaphase II are found to lag at the spindle equator and < 10% of the laggards missegregate and give rise to aneuploid gametes. Our results demonstrate that aberrant kinetochore–microtubule attachments are not corrected at the metaphase stage of the second meiotic division. Thus, the accuracy of the chromosome segregation process in mouse oocytes during meiosis II is ensured by an efficient correction process acting at the anaphase stage.

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Section: Resultsmentioning

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Post‐metaphase correction of aberrant kinetochore‐microtubule attachments in mammalian eggs

et al. 2019

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Section: Discussionsupporting

confidence: 53%

“…This conclusion is further supported by the fact that loss of CDK2 does not affect somatic cells but leads to sterility due to failure to enter meiosis I [68]. Cell type specificity is also seen for cyclin A2, which is required in hematopoetic stem cells, fibroblasts, and female meiosis, but not in other tissues [21,69,70].Overall, our data show that cyclin B3 is an M-phase cyclin with a singular role in oocyte meiosis, probably due to the specificities of meiotic cell cycle regulation in this huge cell. A key challenge now will be defining which set of substrates needs to be phosphorylated by cyclin B3-CDK complexes to bring about proper meiotic progression.…”

supporting

confidence: 53%

“…In female mice, cyclin B3 was speculated to be required for meiotic initiation because its mRNA is substantially upregulated as oogonia cease mitotic proliferation and enter meiotic prophase I [20]. RNAi-mediated knockdown of cyclin B3 to ~30% of wild-type levels in cultured mouse oocytes perturbed progression through meiosis I [21]. However, the molecular basis of the inhibition of meiotic progression was not defined and off-target effects of the RNAi could not be excluded, so the function of cyclin B3 in oocyte meiosis remained unclear.…”

Section: Introductionmentioning

confidence: 99%

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Cyclin B3 promotes APC/C activation and anaphase I onset in oocyte meiosis

Bouftas

Keeney

et al. 2018

Preprint

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As obligate kinase partners, cyclins control the switch-like cell cycle transitions that orchestrate orderly duplication and segregation of genomes. Meiosis, the cell division that generates gametes for sexual reproduction, poses unique challenges because two rounds of chromosome segregation must be executed without intervening DNA replication. Mammalian cells express numerous, temporally regulated cyclins, but how these proteins collaborate to control meiosis remains poorly understood. Here, we delineate an essential function for mouse cyclin B3 in the first meiotic division of oocytes. Females genetically ablated for cyclin B3 are viable, indicating the protein is dispensable for mitotic divisions, but are sterile. Mutant oocytes appear normal until metaphase I but then display a highly penetrant failure to transition to anaphase I. They arrest with hallmarks of defective APC/C activation, including no separase activity and high MPF, cyclin B1, and securin levels. Partial APC/C activation occurs, however, as exogenously expressed APC/C substrates can be degraded and arrest can be suppressed by inhibiting MPF kinase. Cyclin B3 is itself targeted for degradation by the APC/C. Cyclin B3 forms active kinase complexes with CDK1, and meiotic progression requires cyclin B3-associated kinase activity. Collectively, our findings indicate that cyclin B3 is essential for oocyte meiosis because it fine-tunes APC/C activity as a kinase-activating CDK partner. Cyclin B3 homologs from frog, zebrafish, and fruitfly rescue meiotic progression in cyclin B3-deficient mouse oocytes, indicating conservation of the biochemical properties and possibly cellular functions of this germline-critical cyclin. IntroductionEukaryotic cell division depends on oscillations of cyclindependent kinases (CDKs) associated with specific cyclins [1][2][3][4]. In vertebrate somatic cells, progression from G1 into S phase, G2, and mitosis depends on the cyclin D family, followed by the cyclin E, A, and B families [4]. Ordered CDK activity likewise governs progression through meiosis: chromosome condensation, congression, and alignment require a rise in cyclin B-CDK1 activity, then anaphase onset and chromosome segregation are driven by sudden inactivation of cyclin B-CDK1 by the anaphase promoting complex/ cyclosome (APC/C), an E3 ubiquitin ligase that targets substrates for degradation by the 26S proteasome [5]. Cyclin B-CDK1 activity re-accumulates following its depletion, but meiotic cells have the challenge of not inducing DNA replication during the period of low cyclin B-CDK1 activity between meiosis I and II [6,7]. The roles of specific cyclins in shaping CDK oscillations and thus in determining the orderly progression of meiosis remain poorly understood, particularly in mammalian oocytes.In this context, cyclin B3 is particularly enigmatic. Cyclin B3 belongs to a separate family with characteristics of both A-and B-type cyclins [8,9] and is evolutionarily conserved from early metazoans to human [10]. Ciona intestinalis cyclin B3 counteracts zyg...

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Overexpression of cyclin A1 promotes meiotic resumption but induces premature chromosome separation in mouse oocyte

Dong

Ouyang

et al. 2020

Journal Cellular Physiology

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Mammalian cyclin A1 is prominently expressed in testis and essential for meiosis in the male mouse, however, it shows weak expression in ovary, especially during oocyte maturation. To understand why cyclin A1 behaves in this way in the oocyte, we investigated the effect of cyclin A1 overexpression on mouse oocyte meiotic maturation. Our results revealed that cyclin A1 overexpression triggered meiotic

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Cyclin A2 modulates kinetochore–microtubule attachment in meiosis II

Cited by 31 publications

References 69 publications

Post‐metaphase correction of aberrant kinetochore‐microtubule attachments in mammalian eggs

Post‐metaphase correction of aberrant kinetochore‐microtubule attachments in mammalian eggs

Cyclin B3 promotes APC/C activation and anaphase I onset in oocyte meiosis

Overexpression of cyclin A1 promotes meiotic resumption but induces premature chromosome separation in mouse oocyte

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