title: Caf1 regulates translocation of ribonucleotide reductase by releasing nucleoplasmic Spd1-Suc22 assembly.
abstract: Appropriate supply of deoxyribonucleotides by the ribonucleotide reductase (RNR) complex is essential for DNA replication and repair. One recent model for the RNR activation in Schizosaccharomyces pombe is translocation of the regulatory subunit Suc22 from the nucleoplasm to the cytoplasm. The RNR inhibitory protein Spd1, which retains Suc22 in the nucleoplasm, is rapidly degraded upon DNA-replication stress, resulting in release of Suc22 to form the active RNR complex in the cytoplasm. Here, we show that Caf1, a component of the Ccr4-Not complex, is responsible for resistance of the replication stress and control of the Suc22 translocation. Caf1 is required not only for the stress-induced translocation of Suc22 from nucleoplasm to cytoplasm but also for the degradation of nucleoplasmic Spd1. DNA-replication stress appears to allow Caf1 to interact with Suc22, resulting in release of the nucleoplasmic Spd1-Suc22 assembly. Taken together, these results suggest a novel function of Caf1 as a key regulator in the stress-induced RNR activation.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Takahashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kontani
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Araki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Katada
mesh_terms: D021581:Active Transport, Cell Nucleus; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000201:enzymology*; D003593:Cytoplasm / Q000201:enzymology; D004261:DNA Replication; D006918:Hydroxyurea / Q000633:toxicity; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology; D012264:Ribonucleotide Reductases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
chemical_list: C519160:Ccr4 protein, S pombe; D018797:Cell Cycle Proteins; C479134:Hba1 protein, S pombe; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C102445:Spd1 protein, S pombe; D012264:Ribonucleotide Reductases; C080927:SUC22 protein, S pombe; D006918:Hydroxyurea