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

Author:

Strauss Bernhard12,Harrison Andrew12ORCID,Coelho Paula Almeida3ORCID,Yata Keiko12ORCID,Zernicka-Goetz Magdalena14,Pines Jonathon125ORCID

Affiliation:

1. The Gurdon Institute, Cambridge, England, UK

2. Department of Zoology, University of Cambridge, Cambridge, England, UK

3. Department of Genetics, University of Cambridge, Cambridge, England, UK

4. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, England, UK

5. The Institute of Cancer Research, London, England, UK

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.

Funder

Wellcome Trust

Medical Research Council

Cancer Research UK

Publisher

Rockefeller University Press

Subject

Cell Biology

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