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Cyclin B1 is essential for mitosis in mouse embryos, and its nuclear export sets the time for mitosis

Strauss, Bernhard and Harrison, Andrew and Almeida Coelho, Paula and Yata, Keiko and Zernicka-Goetz, Magdalena and Pines, Jonathon (2018) Cyclin B1 is essential for mitosis in mouse embryos, and its nuclear export sets the time for mitosis. Journal of Cell Biology, 217 (1). pp. 179-193. ISSN 0021-9525. PMCID PMC5748970. https://resolver.caltech.edu/CaltechAUTHORS:20190408-111046720

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Abstract

There is remarkable redundancy between the Cyclin–Cdk complexes that comprise the cell cycle machinery. None of the mammalian A-, D-, or E-type cyclins are required in development until implantation, and only Cdk1 is essential for early cell divisions. Cyclin B1 is essential for development, but whether it is required for cell division is contentious. Here, we used a novel imaging approach to analyze Cyclin B1–null embryos from fertilization onward. We show that Cyclin B1−/− embryos arrest in G2 phase after just two divisions. This is the earliest arrest of any Cyclin known and places Cyclin B1 with cdk1 as the essential regulators of the cell cycle. We reintroduced mutant proteins into this genetically null background to determine why Cyclin B1 is constantly exported from the nucleus. We found that Cyclin B1 must be exported from the nucleus for the cell to prevent premature entry to mitosis, and retaining Cyclin B1–Cdk1 at the plasma membrane precludes entry to mitosis.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1083/jcb.201612147DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748970/PubMed CentralArticle
ORCID:
AuthorORCID
Harrison, Andrew0000-0002-3778-8415
Almeida Coelho, Paula0000-0003-0614-7575
Yata, Keiko0000-0001-7648-4898
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Pines, Jonathon0000-0002-5227-6004
Additional Information:© 2018 Strauss et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). Submitted: 20 December 2016. Revised: 2 August 2017. Accepted: 21 September 2017. We are very grateful to Jane Kirk and Tim Hunt for the gift of the Cyclin B1^(+/−) and Cyclin B2^(−/−) mouse strains. We thank all members of both our laboratories for help and advice. This work was supported by a Wellcome Trust Senior Fellowship to M. Zernicka-Goetz and subsequently by a program grant from the Medical Research Council to J. Pines. Both M. Zernicka-Goetz and J. Pines acknowledge core funding provided by the Wellcome Trust (092096) and Cancer Research UK (C6946/A14492). The authors declare no competing financial interests.
Funders:
Funding AgencyGrant Number
Wellcome Trust092096
Medical Research Council (UK)UNSPECIFIED
Cancer Research UKC6946
Cancer Research UKA14492
Issue or Number:1
PubMed Central ID:PMC5748970
Record Number:CaltechAUTHORS:20190408-111046720
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190408-111046720
Official Citation:Cyclin B1 is essential for mitosis in mouse embryos, and its nuclear export sets the time for mitosis Bernhard Strauss, Andrew Harrison, Paula Almeida Coelho, Keiko Yata, Magdalena Zernicka-Goetz, Jonathon Pines J Cell Biol Jan 2018, 217 (1) 179-193; DOI: 10.1083/jcb.201612147
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94570
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Apr 2019 15:19
Last Modified:03 Oct 2019 21:05

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