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The cohesin release factor Wapl interacts with Bub3 to govern SAC activity in female meiosis I. Zhou C et al. (2020) During mitotic prophase, cohesins are removed from chromosome arms by Wapl to ensure faithful sister chromatid separation. However, during female meiosis I, the resolution of chiasmata requires the proteolytic cleavage of cohesin subunit Rec8 along chromosome arms by Separase to separate homologs, and thus the role of Wapl remained unknown. Here, we report that Wapl functions as a regulator of spindle assembly checkpoint (SAC) to prevent aneuploidy in meiosis I. Depletion of Wapl accelerates meiotic progression, inactivates SAC, and causes meiotic defects such as aberrant spindle/chromosome structure and incorrect kinetochore-microtubule (K-MT) attachment, consequently leading to aneuploid eggs. Notably, we identify Bub3 as a binding partner of Wapl by immunoprecipitation and mass spectrometry analysis. We further determine that Wapl controls the SAC activity by maintaining Bub3 protein level and document that exogenous Bub3 restores the normal meiosis in Wapl-depleted oocytes. Together, our findings uncover unique, noncanonical roles for Wapl in mediating control of the SAC in female meiosis I.//////////////////Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis. Li M et al. In mitosis, the spindle assembly checkpoint (SAC) prevents anaphase onset until all chromosomes have been attached to the spindle microtubules and aligned correctly at the equatorial metaphase plate. The major checkpoint proteins in mitosis consist of mitotic arrest-deficient (Mad)1-3, budding uninhibited by benzimidazole (Bub)1, Bub3, and monopolar spindle 1(Mps1). During meiosis, for the formation of a haploid gamete, two consecutive rounds of chromosome segregation occur with only one round of DNA replication. To pull homologous chromosomes to opposite spindle poles during meiosis I, both sister kinetochores of a homologue must face toward the same pole which is very different from mitosis and meiosis II. As a core member of checkpoint proteins, the individual role of Bub3 in mammalian oocyte meiosis is unclear. In this study, using overexpression and RNA interference (RNAi) approaches, we analyzed the role of Bub3 in mouse oocyte meiosis. Our data showed that overexpressed Bub3 inhibited meiotic metaphase-anaphase transition by preventing homologous chromosome and sister chromatid segregations in meiosis I and II, respectively. Misaligned chromosomes, abnormal polar body and double polar bodies were observed in Bub3 knock-down oocytes, causing aneuploidy. Furthermore, through cold treatment combined with Bub3 overexpression, we found that overexpressed Bub3 affected the attachments of microtubules and kinetochores during metaphase-anaphase transition. We propose that as a member of SAC, Bub3 is required for regulation of both meiosis I and II, and is potentially involved in kinetochore-microtubule attachment in mammalian oocytes.
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Identifying new human oocyte marker genes: a microarray approach. Gasca S et al. The efficacy of classical IVF techniques is still impaired by poor implantation and pregnancy rates after embryo transfer. This is mainly due to a lack of reliable criteria for the selection of embryos with sufficient development potential. Several studies have provided evidence that some gene expression levels could be used as objective markers of oocyte and embryo competence and capacity to sustain a successful pregnancy. These analyses usually use reverse transcription-polymerase chain reaction to look at small sets of pre-selected genes. However, microarray approaches allow the identification of a wider range of cellular marker genes which could include additional and perhaps more suitable genes that could serve as embryo selection markers. Microarray screenings of around 30,000 genes on U133P Affymetrix(trade mark)gene chips made it possible to establish the expression profile of these genes as well as other related genes in human oocytes and cumulus cells. This study identifies new potential regulators and marker genes such as BARD1, RBL2, RBBP7, BUB3 or BUB1B, which are involved in oocyte maturation.
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