Cdc14p/FEAR pathway controls segregation of nucleolus in S. cerevisiae by facilitating condensin targeting to rDNA chromatin in anaphase.
The condensin complex is the chief molecular machine of mitotic chromosome condensation. Nucleolar concentration of condensin in mitosis was previously shown to correlate with proficiency of rDNA condensation and segregation. To uncover the mechanisms facilitating this targeting we conducted a screen for mutants that impair mitotic condensin congression to the nucleolus. Mutants in the cdc14, esp1 and cdc5 genes, which encode FEAR-network components, showed the most prominent defects in mitotic condensin localization. We established that Cdc14p activity released by the FEAR pathway was required for proper condensin-to-rDNA targeting in anaphase. The MEN pathway was dispensable for condensin-to-rDNA targeting, however MEN-mediated release of Cdc14p later in anaphase allowed for proper, albeit delayed, condensin targeting to rDNA and successful segregation of nucleolus in the slk19 FEAR mutant. Although condensin was physically dislodged from rDNA in the cdc14 mutant, it was properly assembled, phosphorylated and chromatin-bound, suggesting that condensin was mis-targeted but active. This study identifies a novel pathway promoting condensin targeting to a specific chromosomal address, the rDNA locus.
Wang
Bi-Dar
BD
NIH, NICHD, LGRD, Bethesda, Maryland 20892, USA.
Yong-Gonzalez
Vladimir
V
Strunnikov
Alexander V
AV
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000705:Anaphase / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D018390:Gene Targeting; D008938:Mitosis / Q000502:physiology*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D064247:Separase; D015398:Signal Transduction / Q000235:genetics
C074860:CDC14 protein, S cerevisiae; C513239:CEF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002843:Chromatin; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C108312:condensin complexes; D017027:Protein Tyrosine Phosphatases; D010450:Endopeptidases; C577986:ESP1 protein, S cerevisiae; D064247:Separase; D000251:Adenosine Triphosphatases