Lack of Cyclin B1 in zebrafish causes lengthening of G2 and M phases

An essential part of the Mitosis Promoting Factor, Cyclin B1 is indispensable for cells to enter mitosis. We report here that the zebrafish early arrest mutant specter is a loss-of-function mutation in the сyclin B1 gene. cyclin B1 is maternally transcribed in zebrafish, and the zygotic phenotype is apparent by early segmentation. Lack of zygotic Cyclin B1 does not stop cells from dividing, rather it causes an abnormal and elongated progression through the G2 and M phases of the cell cycle. Many mutant cells show signs of chromosomal instability or enter apoptosis. Using CRISPR-mediated gene editing, we produced a more severe gain-of-function mutation confirming that specter is the result of nonfunctional Cyclin B1. Although also a recessive phenotype, this new mutation produces an alternative splice-form of cyclin B1 mRNA, whose product lacks several key components for Cyclin B1, but not the Cdk1-binding domain. This mutant form of Cyclin B1 completely prevents cell division. We conclude that, although Cyclin B1 is critical for cells to enter mitosis, another cell cycle protein may be cooperating with Cdk1 at the G2/M checkpoint to sustain a partly functional Mitosis Promoting Factor. [Display omitted] •The specter mutant is the result of a mutation in the gene cyclin B1.•Loss of zygotic Cyclin B1 does not prevent cells from dividing.•G2 and M phases are longer in the specter mutant.•Many specter mutant cells exhibit chromosomal abnormalities.