Abstract

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.

Authors	Zhou, Chenxi; Hancock, Janelle L; Khanna, Kum Kum; Homer, Hayden A
Journal	Journal of cell science
Pages
Volume	132
Date	1/08/2019
Grant ID
Funding Body	Professor Christopher Chen Endowment Fund
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1242/jcs.233379