Metaphase I Arrest upon Activation of the Mad2-Dependent Spindle Checkpoint in Mouse Oocytes

Wassmann, Katja; Niault, Théodora; Maro, Bernard

doi:10.1016/j.cub.2003.08.052

Cited by 194 publications

(198 citation statements)

References 43 publications

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“…On the face of it, it is perplexing that all of the components critical for operation of this loop could potentially be present in MI, yet this feedback pathway does not appear to operate at this cell cycle stage. This is most likely due to the fact that the spindle checkpoint is operative in MI (Wassmann et al, 2003), but not during MII arrest (Tsurumi et al, 2004). This checkpoint results in profound APC inhibition until the metaphase I plate is formed, allowing constitutively high Cdc2 kinase activity and consequently rapid Emi2 turnover.…”

Section: Differential Control Of the Apc In MI And Miimentioning

confidence: 99%

Cdc2 and Mos Regulate Emi2 Stability to Promote the Meiosis I–Meiosis II Transition

Tang

Guo

et al. 2008

MBoC

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The transition of oocytes from meiosis I (MI) to meiosis II (MII) requires partial cyclin B degradation to allow MI exit without S phase entry. Rapid reaccumulation of cyclin B allows direct progression into MII, producing a cytostatic factor (CSF)-arrested egg. It has been reported that dampened translation of the anaphase-promoting complex (APC) inhibitor Emi2 at MI allows partial APC activation and MI exit. We have detected active Emi2 translation at MI and show that Emi2 levels in MI are mainly controlled by regulated degradation. Emi2 degradation in MI depends not on Ca2+/calmodulin-dependent protein kinase II (CaMKII), but on Cdc2-mediated phosphorylation of multiple sites within Emi2. As in MII, this phosphorylation is antagonized by Mos-mediated recruitment of PP2A to Emi2. Higher Cdc2 kinase activity in MI than MII allows sufficient Emi2 phosphorylation to destabilize Emi2 in MI. At MI anaphase, APC-mediated degradation of cyclin B decreases Cdc2 activity, enabling Cdc2-mediated Emi2 phosphorylation to be successfully antagonized by Mos-mediated PP2A recruitment. These data suggest a model of APC autoinhibition mediated by stabilization of Emi2; Emi2 proteins accumulate at MI exit and inhibit APC activity sufficiently to prevent complete degradation of cyclin B, allowing MI exit while preventing interphase before MII entry.

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Section: Differential Control Of the Apc In MI And Miimentioning

confidence: 99%

Cdc2 and Mos Regulate Emi2 Stability to Promote the Meiosis I–Meiosis II Transition

Tang

Guo

et al. 2008

MBoC

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“…However, maternal expression of these genes could mask earlier requirements during embryogenesis, and treatment of early Drosophila embryos with nocodazole does result in mitotic delays (Yu et al, 1998). Evidence for a functional spindle checkpoint during meiosis in mouse oocytes suggests that the checkpoint machinery is present in early mammalian embryos (Wassmann et al, 2003). Thus, it seems likely that other early embryos will be found to use, perhaps to varying degrees, a spindle checkpoint during early embryonic cell cycles.…”

Section: A Functional Spindle Checkpoint Mechanism In An Early Animalmentioning

confidence: 99%

A Spindle Checkpoint Functions during Mitosis in the EarlyCaenorhabditis elegansEmbryo

Encalada

Willis

Lyczak

et al. 2005

MBoC

118

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During mitosis, chromosome segregation is regulated by a spindle checkpoint mechanism. This checkpoint delays anaphase until all kinetochores are captured by microtubules from both spindle poles, chromosomes congress to the metaphase plate, and the tension between kinetochores and their attached microtubules is properly sensed. Although the spindle checkpoint can be activated in many different cell types, the role of this regulatory mechanism in rapidly dividing embryonic animal cells has remained controversial. Here, using time-lapse imaging of live embryonic cells, we show that chemical or mutational disruption of the mitotic spindle in early Caenorhabditis elegans embryos delays progression through mitosis. By reducing the function of conserved checkpoint genes in mutant embryos with defective mitotic spindles, we show that these delays require the spindle checkpoint. In the absence of a functional checkpoint, more severe defects in chromosome segregation are observed in mutants with abnormal mitotic spindles. We also show that the conserved kinesin CeMCAK, the CENP-F-related proteins HCP-1 and HCP-2, and the core kinetochore protein CeCENP-C all are required for this checkpoint. Our analysis indicates that spindle checkpoint mechanisms are functional in the rapidly dividing cells of an early animal embryo and that this checkpoint can prevent chromosome segregation defects during mitosis. INTRODUCTIONDuring mitosis, some microtubules emanating from bipolar microtubule organizing centers grow toward chromosomes and attach to specialized chromosomal regions called kinetochores (Skibbens and Hieter, 1998;Cleveland et al., 2003). Once captured, sister chromatids are segregated, one to each of two daughter cells. Eukaryotic cells have evolved a mechanism called the spindle checkpoint, to monitor chromosomal segregation and increase the fidelity of mitosis (reviewed in Gardner and Burke, 2000;McIntosh et al., 2002). Until spindle microtubules from both poles capture and align all sister chromatid pairs at a metaphase plate, the spindle checkpoint produces a delay in the onset of anaphase. If this delay is bypassed by reducing checkpoint function, anaphase starts prematurely, and daughter cells may receive unequal complements of chromosomes. Such genomic instability can result in lethality and in tumorigenesis (Hartwell and Kastan, 1994;Basu et al., 1999).Originally identified and characterized in Saccharomyces cerevisiae, seven spindle assembly checkpoint genes (MAD1, MAD2, MAD3, BUB1, BUB2, BUB3, and MPS1) are known to function at kinetochores to inhibit anaphase onset, or to mediate mitotic exit in the presence of spindle abnormalities (Hoyt et al., 1991;Li and Murray, 1991). Mutations in these genes reduce or eliminate the cell cycle delays that normally occur after treatment with microtubule depolymerizing drugs (Wang and Burke, 1995;Pangilinan and Spencer, 1996). Bub1 and Bub3 form a protein kinase complex that, in concert with Mps1, functions at kinetochores upstream of Mad1 and Mad2 (Roberts et al., 1994;H...

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“…Consistent with this, BUB1 is in a phosphorylated state throughout this time, typical of when the SAC activated. In contrast, MAD2 is present early in prometaphase (Wassmann et al 2003). MAD2 may also have important functions in the absence of spindle damage, as progression through meiosis I was accelerated (Tsurumi et al 2004) and there was an increase in chromosome segregation errors when MAD2 was depleted (Homer et al 2005b).…”

Section: Kinetochoreymicrotubule Interactions Do Not Occur In Oocytesmentioning

confidence: 98%

“…MAD2, which normally disappears from the kinetochores during prometaphase, relocalizes upon spindle damage induced by nocodazole (Wassmann et al 2003). Meiotic progression is also affected, as the drop of MPF between meiosis I and II is inhibited and anaphase I onset is delayed (Brunet et al 2003).…”

Section: Kinetochoreymicrotubule Interactions Do Not Occur In Oocytesmentioning

confidence: 99%

Spindle assembly in the oocytes of mouse and Drosophila – similar solutions to a problem

Doubilet

McKim

2007

Chromosome Res

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In the oocytes of many organisms a bipolar spindle is assembled in the absence of centrosomes. In this article we review how this occurs in two model organisms, Drosophila melanogaster and Mus musculus. Common themes include an important role for the chromosomes but paradoxically, organization of a bipolar spindle may not involve kinetochore microtubules. Some comparisons are not yet possible, however, since the same genes have usually not been studied in both systems.

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Metaphase I Arrest upon Activation of the Mad2-Dependent Spindle Checkpoint in Mouse Oocytes

Cited by 194 publications

References 43 publications

Cdc2 and Mos Regulate Emi2 Stability to Promote the Meiosis I–Meiosis II Transition

Cdc2 and Mos Regulate Emi2 Stability to Promote the Meiosis I–Meiosis II Transition

A Spindle Checkpoint Functions during Mitosis in the EarlyCaenorhabditis elegansEmbryo

Spindle assembly in the oocytes of mouse and Drosophila – similar solutions to a problem

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