title: The nucleolar phosphatase Cdc14B is dispensable for chromosome segregation and mitotic exit in human cells.
abstract: In yeast, the protein phosphatase Cdc14 promotes chromosome segregation, mitotic exit, and cytokinesis by reversing M-phase phosphorylations catalyzed by Cdk1. A key feature of Cdc14 regulation is its sequestration within the nucleolus, which restricts its access to potential substrates for much of the cell cycle. Mammals also possess a nucleolar Cdc14 homolog, termed Cdc14B, but its roles during mitosis and cell division remain speculative. Here we analyze Cdc14B's subcellular dynamics during mitosis and rigorously test its functional contributions to cell division through homozygous disruption of the Cdc14B locus in human somatic cells. While Cdc14B is initially released from nucleoli at the start of mitosis, the phosphatase quickly redistributes onto segregating sister chromatids during anaphase. This relocalization is mainly driven by Cdk1 inactivation, as pharmacologic inhibition of Cdk1 in prometaphase cells redirects Cdc14B onto chromosomes. However, in sharp contrast to yeast cdc14 mutants, human Cdc14B(Delta/Delta) cells were viable and lacked defects in spindle assembly, anaphase progression, mitotic exit, and cytokinesis, and continued to segregate ribosomal DNA repeats with near-normal proficiency. Our findings reveal substantial divergence in mitotic regulation between yeast and mammalian cells, as the latter possess efficient mechanisms for completing late M-phase events in the absence of a nucleolar Cdc14-related phosphatase.
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Eli
authors.initials: E
authors.lastname: Berdougo
authors.forename: Maxence V
authors.initials: MV
authors.lastname: Nachury
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jackson
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Jallepalli
mesh_terms: D000705:Anaphase / Q000235:genetics; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D002466:Cell Nucleolus / Q000201:enzymology* / Q000235:genetics; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D020090:Chromosome Segregation / Q000502:physiology*; D048749:Cytokinesis / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D012854:Sister Chromatid Exchange / Q000235:genetics; D013045:Species Specificity; D008941:Spindle Apparatus / Q000378:metabolism; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004275:DNA, Ribosomal; D016203:CDC2 Protein Kinase; D010744:Phosphoric Monoester Hydrolases; C474200:CDC14B protein, human; D054637:Dual-Specificity Phosphatases