Polo kinase regulates mitotic chromosome condensation by hyperactivation of condensin DNA supercoiling activity.
A defining feature of mitosis is the reorganization of chromosomes into highly condensed structures capable of withstanding separation and large-scale intracellular movements. This reorganization is promoted by condensin, an evolutionarily conserved multisubunit ATPase. Here we show, using budding yeast, that condensin is regulated by phosphorylation specifically in anaphase. This phosphorylation depends on several mitotic regulators, and the ultimate effector is the Polo kinase Cdc5. We demonstrate that Cdc5 directly phosphorylates all three regulatory subunits of the condensin complex in vivo and that this causes a hyperactivation of condensin DNA supercoiling activity. Strikingly, abrogation of condensin phosphorylation is incompatible with viability, and cells expressing condensin mutants that have a reduced ability to be phosphorylated in vivo are defective in anaphase-specific chromosome condensation. Our results reveal the existence of a regulatory mechanism essential for the promotion of genome integrity through the stimulation of chromosome condensation in late mitosis.
St-Pierre
Julie
J
Institute for Research in Immunology and Cancer, Université de Montréal, Station Centre-Ville, Quebec, Canada.
Douziech
Mélanie
M
Bazile
Franck
F
Pascariu
Mirela
M
Bonneil
Eric
E
Sauvé
Véronique
V
Ratsima
Hery
H
D'Amours
Damien
D
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000705:Anaphase / Q000502:physiology*; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D015825:Chromosomes, Fungal / Q000378:metabolism*; D004278:DNA, Superhelical / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D018797:Cell Cycle Proteins; D004278:DNA, Superhelical; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; C108312:condensin complexes; D011494:Protein Kinases; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C081927:CDC5 protein, S cerevisiae; D016203:CDC2 Protein Kinase; D000251:Adenosine Triphosphatases