Abstract
Zinc finger proteins are a massive, diverse family of proteins that serve a wide variety of biological functions. However, the roles of them during meiosis are not yet clearly defined. Here, we report that Zfp207 localizes at the kinetochores during mouse oocyte meiotic maturation. Depletion of Zfp207 leads to a significantly higher proportion of impaired spindle organization and misaligned chromosomes in oocytes. This is coupled with the defective kinetochore-microtubule attachments, and resultantly increasing incidence of aneuploid metaphase II eggs. The precocious polar body extrusion and escape of metaphase I arrest induced by nocodazole treatment in Zfp207-depleted oocytes indicates that Zfp207 is essential for activation of SAC (Spindle Assembly Checkpoint) activity. Notably, we find that Zfp207 binds to Bub3 to form a complex and maintains its protein level in oocytes, and that overexpression of Bub3 is able to partially rescue the occurrence of aneuploid eggs in Zfp207-depleted oocytes. Collectively, we identify Zfp207 as a novel Bub3 binding protein in oocytes which plays an important role in controlling meiotic chromosome alignment and SAC function.
Highlights
High-fidelity chromosome segregation ensures proper distribution of genetic material during cell division in both mitosis and meiosis [1]
Fully-grown germinal vesicle (GV) oocytes were microinjected with control and Zfp207-specific morpholinos and arrested in medium supplemented with milrinone for 20 h, allowing enough time to deplete the endogenous Zfp207
The highly conserved spindle assembly checkpoint mechanisms and components have been widely studied in mitosis, whereas the functional roles and components of SAC in meiosis are still not fully clear
Summary
High-fidelity chromosome segregation ensures proper distribution of genetic material during cell division in both mitosis and meiosis [1]. To achieve faithful chromosome segregation, eukaryotic cells develop a high-fidelity surveillance system referred to as SAC (spindle assembly checkpoint) to prevent chromosome missegregation and aneuploidy by delaying anaphase onset until all kinetochores are successfully attached to the spindle microtubules with the proper tension at the metaphase plate [4,5,6,7,8]. Once chromosome is properly aligned at metaphase plate with appropriate tension by the spindle, SAC pathway is shut down and Cdc is released to activate APC/C, which ubiquitinates Securin and Cyclin B, leading to the activation of Separase to remove the Cohesin complex from chromosome and onset of anaphase [9, 11, 12]
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