title: The yeast polo kinase Cdc5 regulates the shape of the mitotic nucleus.
abstract: Abnormal nuclear size and shape are hallmarks of aging and cancer. 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. 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. 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, plays a role in regulating nuclear morphology and NE expansion.
authors.affiliation: Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Alison D
authors.initials: AD
authors.lastname: Walters
authors.affiliation: Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: May
authors.affiliation: Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Emma S
authors.initials: ES
authors.lastname: Dauster
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Bertrand P
authors.initials: BP
authors.lastname: Cinquin
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Smith
authors.affiliation: Institute for Research in Immunology and Cancer and Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Xavier
authors.initials: X
authors.lastname: Robellet
authors.affiliation: Institute for Research in Immunology and Cancer and Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Damien
authors.initials: D
authors.lastname: D'Amours
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Larabell
authors.affiliation: Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: ornac@helix.nih.gov.
authors.forename: Orna
authors.initials: O
authors.lastname: Cohen-Fix
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D020090:Chromosome Segregation; D004275:DNA, Ribosomal / Q000378:metabolism; D008938:Mitosis; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D004718:Saccharomycetales / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004275:DNA, Ribosomal; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases; C081927:CDC5 protein, S cerevisiae