Dpb11, which interacts with DNA polymerase II (epsilon) in Saccharomyces cerevisiae, has a dual role in S-phase progression and at a cell cycle checkpoint

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-12, Vol.92 (25), p.11791-11795
• Main Authors: Araki, H. (Osaka University, Osaka, Japan.), Leem, S.H, Phongdara, A, Sugino, A
• Format: Article
• Language: English
• Subjects: ADN; Amino Acid Sequence; Cell cycle; Cell Cycle - physiology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell growth; Cell nucleus; COMPOSICION QUIMICA; COMPOSITION CHIMIQUE; Daughter cells; Deoxyribonucleic acid; DIVISION CELLULAIRE; DIVISION CELULAR; DNA; DNA Polymerase II - genetics; DNA Polymerase II - metabolism; DNA replication; DNA-Binding Proteins; Dose-Response Relationship, Radiation; Flow Cytometry; Fungal Proteins - genetics; GENE; Gene Dosage; GENES; Genes, Fungal; Genes, Suppressor; Genetic mutation; Genetics; Hydroxyurea - pharmacology; Methyl Methanesulfonate - pharmacology; Molecular Sequence Data; Mother cells; MUTACION INDUCIDA; MUTANT; MUTANTES; Mutation; MUTATION PROVOQUEE; Phenotype; Plasmids; Protein Binding; PROTEINAS AGLUTINANTES; PROTEINE DE LIAISON; S Phase - physiology; SACCHAROMYCES CEREVISIAE; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - physiology; Saccharomyces cerevisiae Proteins; Schizosaccharomyces pombe; Schizosaccharomyces pombe Proteins; SECUENCIA NUCLEICA; Sequence Homology, Amino Acid; SEQUENCE NUCLEIQUE; TRANSFERASAS; TRANSFERASE; Transglutaminases; Ultraviolet Rays - adverse effects; Yeast
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.25.11791

DPB11, a gene that suppresses mutations in two essential subunits of Saccharomyces cerevisiae DNA polymerase II (epsilon) encoded by POL2 and DPB2, was isolated on a multicopy plasmid. The nucleotide sequence of the DPB11 gene revealed an open reading frame predicting an 87-kDa protein. This protein is homologous to the Schizosaccharomyces pombe rad4+/cut5+ gene product that has a cell cycle checkpoint function. Disruption of DPB11 is lethal, indicating that DPB11 is essential for cell proliferation. In thermosensitive dpb11-1 mutant cells, S-phase progression is defective at the nonpermissive temperature, followed by cell division with unequal chromosomal segregation accompanied by loss of viability. dpb11-1 is synthetic lethal with any one of the dpb2-1, pol2-11, and pol2-18 mutations at all temperatures. Moreover, dpb11 cells are sensitive to hydroxyurea, methyl methanesulfonate, and UV irradiation. These results strongly suggest that Dpb11 is a part of the DNA polymerase II complex during chromosomal DNA replication and also acts in a checkpoint pathway during the S phase of the cell cycle to sense stalled DNA replication