G(1)/S CDK is inhibited to restrain mitotic onset when DNA replication is blocked in fission yeast.
Cyclin-dependent kinase (CDK) Tyr15 phosphorylation plays a major role in regulating G(2)/M CDKs, but the role of this phosphorylation in regulating G(1)/S CDKs is less clear. We have studied the regulation and function of Cdc2-Tyr15 phosphorylation in the fission yeast Schizosaccharomyces pombe G(1)/S CDK Cig2/Cdc2. This complex is subject to high level Cdc2-Tyr15 phosphorylation inhibiting its kinase activity in hydroxyurea-treated cells blocked in S-phase. We show that this Tyr15 phosphorylation is required to maintain efficient mitotic checkpoint arrest, because Cig2 accumulates during the block and this accumulation can advance mitotic onset. This mitotic induction operates, at least in part, through activation of the normal G(2)/M CDK complex Cdc13/Cdc2. Thus, Tyr15 phosphorylation of G(1)/S CDK complexes is important in the checkpoint control blocking mitotic onset when DNA replication is inhibited.
Zarzov
Patrick
P
Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. zarzov@curie.u-psud.fr
Decottignies
Anabelle
A
Baldacci
Giuseppe
G
Nurse
Paul
P
D016203:CDC2 Protein Kinase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins; D019926:Cyclin B / Q000502:physiology*; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication / Q000187:drug effects / Q000502:physiology*; D004271:DNA, Fungal / Q000096:biosynthesis*; D016193:G1 Phase / Q000502:physiology*; D018816:Genes, cdc; D006918:Hydroxyurea / Q000494:pharmacology; D046911:Macromolecular Substances; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000502:physiology; D011499:Protein Processing, Post-Translational; D016196:S Phase / Q000502:physiology*; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; C080328:Cig2 protein, S pombe; D019926:Cyclin B; D016213:Cyclins; D004271:DNA, Fungal; D046911:Macromolecular Substances; D029702:Schizosaccharomyces pombe Proteins; D019000:Phosphotyrosine; D016203:CDC2 Protein Kinase; D006918:Hydroxyurea