Meiosis poses unique challenges because two rounds of chromosome segregation must be executed without intervening DNA replication. Mammalian cells express numerous temporally regulated cyclins, but how these proteins collaborate to control meiosis remains poorly understood. Here, we show that female mice genetically ablated for cyclin B3 are viable—indicating that the protein is dispensable for mitotic divisions—but are sterile. Mutant oocytes appear normal until metaphase I but then display a highly penetrant failure to transition to anaphase I. They arrest with hallmarks of defective anaphase-promoting complex/cyclosome (APC/C) activation, including no separase activity, high CDK1 activity, and high cyclin B1 and securin levels. Partial APC/C activation occurs, however, as exogenously expressed APC/C substrates can be degraded. Cyclin B3 forms active kinase complexes with CDK1, and meiotic progression requires cyclin B3–associated kinase activity. Cyclin B3 homologues from frog, zebrafish, and fruit fly rescue meiotic progression in cyclin B3–deficient mouse oocytes, indicating conservation of the biochemical properties and possibly cellular functions of this germline-critical cyclin.
B-type cyclins in association with Cdk1 mediate key steps of mitosis and meiosis, by phosphorylating a plethora of substrates. Progression through the meiotic cell cycle requires the execution of two cell divisions named meiosis I and II without intervening S-phase, to obtain haploid gametes. These two divisions are highly asymmetric in the large oocyte. Chromosome segregation in meiosis I and sister chromatid segregation in meiosis II requires the sharp, switch-like inactivation of Cdk1 activity, which is brought about by degradation of B-type cyclins and counteracting phosphatases. Importantly and contrary to mitosis, inactivation of Cdk1 must not allow S-phase to take place at exit from meiosis I. Here, we describe recent studies on the regulation of translation and degradation of B-type cyclins in mouse oocytes, and how far their roles are redundant or specific, with a special focus on the recently discovered oocyte-specific role of cyclin B3.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.