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Comment |
First meiotic anaphase requires Cep55-dependent inhibitory Cdk1 phosphorylation. Zhou C et al. (2019) During mitosis, anaphase is triggered by anaphase-promoting complex (APC)-mediated destruction of securin and cyclin B1, which leads to inactivation of cyclin-dependent kinase 1 (Cdk1). By regulating APC activity, the mitotic spindle assembly checkpoint (SAC) therefore has robust control over anaphase-timing to prevent chromosome mis-segregation. Mammalian oocytes are prone to aneuploidy, the reasons for which, remain obscure. Here, in mouse oocytes, we deplete Cep55, which, in mitosis, is required post-anaphase for the final steps of cytokinesis. We find that Cep55-depleted oocytes progress normally through early meiosis I, but that anaphase I fails due to persistent Cdk1 activity. Unexpectedly, compromised Cdk1 inactivation following Cep55-depletion occurred despite on-time SAC silencing and intact APC-mediated proteolysis. Instead, it was due to inadequate inhibitory Cdk1 phosphorylation consequent upon failure to suppress Cdc25 phosphatase, identifying a proteolysis-independent step necessary for anaphase I. Thus, the SAC in oocytes does not exert exclusive control over anaphase I-initiation, providing new insight into vulnerability to error.//////////////////
Cep55 regulates spindle organization and cell cycle progression in meiotic oocyte. Xu ZY et al. (2015) Cep55 is a relatively novel member of the centrosomal protein family. Here, we show that Cep55 is expressed in mouse oocytes from the germinal vesicle (GV) to metaphase II (MII) stages. Immuostaining and confocal microscopy as well as time lapse live imaging after injection of mRNA encoding fusion protein of Cep55 and GFP identified that Cep55 was localized to the meiotic spindle, especially to the spindle poles at metaphase, while it was concentrated at the midbody in telophase in meiotic oocytes. Knockdown of Cep55 by specific siRNA injection caused the dissociation of γ-tubulin from the spindle poles, resulting in severely defective spindles and misaligned chromosomes, leading to metaphase I arrest and failure of first polar body (PB1) extrusion. Correspondingly, cyclin B accumulation and spindle assembly checkpoint (SAC) activation were observed in Cep55 knockdown oocytes. Our results suggest that Cep55 may act as an MTOC-associated protein regulating spindle organization, and thus cell cycle progression during mouse oocyte meiotic maturation.//////////////////
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