Sister chromatid segregation in meiosis II: Deprotection through phosphorylation

Wassmann, Katja

doi:10.4161/cc.24600

Cited by 33 publications

(34 citation statements)

References 101 publications

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“…The first meiotic division, with the separation of homologous chromosomes is termed reductional division. The second division, which takes place immediately after MI without an intervening S-phase, is equational, with the separation of sister chromatids, similar to mitosis (Schindler, 2011;Wassmann, 2013). Although unique, oocyte meiosis, and especially MII, still appears to adopt many of the same proteins and mechanisms as described for mitosis, with necessary modifications to accommodate their special needs (Liu, 2012).…”

Section: Discussionmentioning

confidence: 99%

Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility

Wang

Teng³

et al. 2015

Journal of Cell Science

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Dynamic protein phosphorylation and dephosphorylation, mediated by a conserved cohort of protein kinases and phosphatases, regulate cell cycle progression. Among the well-known PP2A-like protein phosphatases, protein phosphatase 6 (PP6) has been analyzed in mammalian mitosis, and Aurora A has recently been identified as its key substrate. However, the functions of PP6 in meiosis are still entirely unknown. To identify the physiological role of PP6 in female gametogenesis, Ppp6c F/F mice were first generated and crossed with Zp3-Cre mice to selectively disrupt Ppp6c expression in oocytes. Here, we report for the first time that PP6c is dispensable for oocyte meiotic maturation but essential for exit from meiosis II (MII) after fertilization. Depletion of PP6c caused an abnormal MII spindle and disrupted MII cytokinesis, resulting in zygotes with high risk of aneuploidy and defective early embryonic development, and thus severe subfertility. We also reveal that PP6 inactivation interferes with MII spindle formation and MII exit owing to increased Aurora A activity, and that Aurora A inhibition with MLN8237 can rescue the PP6c depletion phenotype. In conclusion, our findings uncover a hitherto unknown role for PP6 as an indispensable regulator of oocyte meiosis and female fertility.

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Section: Discussionmentioning

confidence: 99%

Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility

Wang

Teng³

et al. 2015

Journal of Cell Science

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“…Thus, the cohesin-complex is an essential structure during cell division. 4 Undoubtedly, cell division is one of the key processes for every tumor cell including AML blasts due to the increased proliferation potential of malignant cells. Interestingly, more recent data suggests that cohesin genes have additional functions within the cell such as doublestrand DNA repair and regulation of transcription.…”

Section: Introductionmentioning

confidence: 99%

Mutations in the cohesin complex in acute myeloid leukemia: clinical and prognostic implications

Thol

Bollin

Gehlhaar

et al. 2014

Blood

171

167

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Key Points• Mutations in genes of the cohesin complex are recurrent mutations in AML with a strong association with NPM1 mutations.• Cohesin gene mutations have no clear prognostic impact in AML patients.Mutations in the cohesin complex are novel, genetic lesions in acute myeloid leukemia (AML) that are not well characterized. In this study, we analyzed the frequency, clinical, and prognostic implications of mutations in STAG1, STAG2, SMC1A, SMC3, and RAD21, all members of the cohesin complex, in a cohort of 389 uniformly treated AML patients by next generation sequencing. We identified a total of 23 patients (5.9%) with somatic mutations in 1 of the cohesin genes. All gene mutations were mutually exclusive, and STAG1 (1.8%), STAG2 (1.3%), and SMC3 (1.3%) were most frequently mutated. Patients with any cohesin complex mutation had lower BAALC expression levels. We found a strong association between mutations affecting the cohesin complex and NPM1.

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“…In mammalian oocytes, this is brought about through the combined action of physical removal of PP2A-B56 through the bipolar tension now applied on sister kinetochores, and the action of I2PP2A/SET, and CYCLIN A2 (Chambon et al 2013;Gomez et al 2007;Lee et al 2008;Touati et al 2012;Wassmann 2013).…”

Section: Holding Sisters Togethermentioning

confidence: 99%

How oocytes try to get it right: spindle checkpoint control in meiosis

Touati

Wassmann

2015

Chromosoma

Self Cite

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The generation of a viable, diploid organism depends on the formation of haploid gametes, oocytes, and spermatocytes, with the correct number of chromosomes. Halving the genome requires the execution of two consecutive specialized cell divisions named meiosis I and II. Unfortunately, and in contrast to male meiosis, chromosome segregation in oocytes is error prone, with human oocytes being extraordinarily "meiotically challenged". Aneuploid oocytes, that are with the wrong number of chromosomes, give rise to aneuploid embryos when fertilized. In humans, most aneuploidies are lethal and result in spontaneous abortions. However, some trisomies survive to birth or even adulthood, such as the well-known trisomy 21, which gives rise to Down syndrome (Nagaoka et al. in Nat Rev Genet 13:493-504, 2012). A staggering 20-25 % of oocytes ready to be fertilized are aneuploid in humans. If this were not bad enough, there is an additional increase in meiotic missegregations as women get closer to menopause. A woman above 40 has a risk of more than 30 % of getting pregnant with a trisomic child. Worse still, in industrialized western societies, child birth is delayed, with women getting their first child later in life than ever. This trend has led to an increase of trisomic pregnancies by 70 % in the last 30 years (Nagaoka et al. in Nat Rev Genet 13:493-504, 2012; Schmidt et al. in Hum Reprod Update 18:29-43, 2012). To understand why errors occur so frequently during the meiotic divisions in oocytes, we review here the molecular mechanisms at works to control chromosome segregation during meiosis. An important mitotic control mechanism, namely the spindle assembly checkpoint or SAC, has been adapted to the special requirements of the meiotic divisions, and this review will focus on our current knowledge of SAC control in mammalian oocytes. Knowledge on how chromosome segregation is controlled in mammalian oocytes may help to identify risk factors important for questions related to human reproductive health.

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Sister chromatid segregation in meiosis II: Deprotection through phosphorylation

Cited by 33 publications

References 101 publications

Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility

Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility

Mutations in the cohesin complex in acute myeloid leukemia: clinical and prognostic implications

How oocytes try to get it right: spindle checkpoint control in meiosis

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