Open AccessFirst meiotic anaphase requires Cep55-dependent inhibitory Cdk1 phosphorylation
Author(s) -
Chenxi Zhou,
Janelle L. Hancock,
Kum Kum Khanna,
Hayden Homer
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.233379
Subject(s) - anaphase , securin , biology , microbiology and biotechnology , anaphase promoting complex , separase , spindle checkpoint , cytokinesis , cyclin dependent kinase 1 , mitosis , cyclin b , cyclin b1 , mitotic exit , chromosome segregation , cell cycle , genetics , spindle apparatus , cyclin , cell division , chromosome , cell , gene
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.