The Yeast Polo Kinase Cdc5 Regulates the Shape of the Mitotic Nucleus

Abnormal nuclear size and shape are hallmarks of aging and cancer [1, 2]. However, the mechanisms regulating nuclear morphology and nuclear envelope (NE) expansion are poorly understood. In metazoans, the NE disassembles prior to chromosome segregation and reassembles at the end of mitosis [3]. In b...

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Published in:	Current biology 2014-12, Vol.24 (23), p.2861-2867
Main Authors:	Walters, Alison D., May, Christopher K., Dauster, Emma S., Cinquin, Bertrand P., Smith, Elizabeth A., Robellet, Xavier, D’Amours, Damien, Larabell, Carolyn A., Cohen-Fix, Orna
Format:	Article
Language:	eng
Subjects:	BASIC BIOLOGICAL SCIENCES Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Nucleolus - genetics Cell Nucleolus - metabolism Cell Nucleus - metabolism Chromosome Segregation DNA, Ribosomal - metabolism Metazoa Mitosis Mutation Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism Saccharomycetales - genetics Saccharomycetales - metabolism
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Summary:	Abnormal nuclear size and shape are hallmarks of aging and cancer [1, 2]. However, the mechanisms regulating nuclear morphology and nuclear envelope (NE) expansion are poorly understood. In metazoans, the NE disassembles prior to chromosome segregation and reassembles at the end of mitosis [3]. In budding yeast, the NE remains intact. The nucleus elongates as chromosomes segregate and then divides at the end of mitosis to form two daughter nuclei without NE disassembly. The budding yeast nucleus also undergoes remodeling during a mitotic arrest; the NE continues to expand despite the pause in chromosome segregation, forming a nuclear extension, or “flare,” that encompasses the nucleolus [4]. The distinct nucleolar localization of the mitotic flare indicates that the NE is compartmentalized and that there is a mechanism by which NE expansion is confined to the region adjacent to the nucleolus. Here we show that mitotic flare formation is dependent on the yeast polo kinase Cdc5. This function of Cdc5 is independent of its known mitotic roles, including rDNA condensation. High-resolution imaging revealed that following Cdc5 inactivation, nuclei expand isometrically rather than forming a flare, indicating that Cdc5 is needed for NE compartmentalization. Even in an uninterrupted cell cycle, a small NE expansion occurs adjacent to the nucleolus prior to anaphase in a Cdc5-dependent manner. Our data provide the first evidence that polo kinase, a key regulator of mitosis [5], plays a role in regulating nuclear morphology and NE expansion. [Display omitted] •Yeast polo kinase Cdc5 regulates compartmentalization of the nuclear envelope (NE)•Cdc5 confines NE expansion to the nucleolar region during a mitotic delay•Cdc5 also affects NE expansion during an uninterrupted cell cycle•Cdc5 affects NE expansion independent of FEAR, MEN, and rDNA condensation The regulation of nuclear morphology is poorly understood. In budding yeast, a mitotic arrest induces a nuclear envelope (NE) extension (flare) adjacent to the nucleolus. Walters et al. show that in the absence of Cdc5 polo kinase activity, the nucleus expands isometrically, without forming a flare. Thus, Cdc5 is required for NE compartmentalization.
ISSN:	0960-9822 1879-0445