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1.
Proc Natl Acad Sci U S A ; 97(6): 2579-84, 2000 Mar 14.
Article in English | MEDLINE | ID: mdl-10716991

ABSTRACT

Two paradigms exist for maintaining order during cell-cycle progression: intrinsic controls, where passage through one part of the cell cycle directly affects the ability to execute another, and checkpoint controls, where external pathways impose order in response to aberrant structures. By studying the mitotic inhibitor Mik1, we have identified evidence for an intrinsic link between unperturbed S phase and mitosis. We propose a model in which S/M linkage can be generated by the production and stabilization of Mik1 protein during S phase. The production of Mik1 during unperturbed S phase is independent of the Rad3- and Cds1-dependent checkpoint controls. In response to perturbed S phase, Rad3-Cds1 checkpoint controls are required to maintain high levels of Mik1, probably indirectly by extending the S phase period, where Mik1 is stable. In addition, we find that Mik1 protein can be moderately induced in response to irradiation of G(2) cells in a Chk1-dependent manner.


Subject(s)
Mitosis , Protein-Tyrosine Kinases/metabolism , S Phase , Schizosaccharomyces pombe Proteins , Checkpoint Kinase 1 , Enzyme Inhibitors/pharmacology , Epitopes/metabolism , Flow Cytometry , G2 Phase , Hydroxyurea/pharmacology , Immunoblotting , Microscopy, Fluorescence , Models, Biological , Phosphoric Monoester Hydrolases/metabolism , Phosphorylation , Protein Kinases/metabolism , Schizosaccharomyces/enzymology , Time Factors
2.
Curr Biol ; 9(23): 1427-30, 1999 Dec 02.
Article in English | MEDLINE | ID: mdl-10607571

ABSTRACT

The COP9/signalosome complex is conserved from plant to mammalian cells. In Arabidopsis, it regulates the nuclear abundance of COP1, a transcriptional repressor of photomorphogenic development [1] [2]. All COP (constitutive photomorphogenesis) mutants inappropriately express genes that are normally repressed in the dark. Eight subunits (Sgn1-Sgn8) of the homologous mammalian complex have been purified [3] [4]. Several of these have been previously identified through genetic or protein interaction screens. No coherent model for COP9/signalosome function has yet emerged, but a relationship with cell-cycle progression by transcriptional regulation, protein localisation or protein stability is possible. Interestingly, the COP9/signalosome subunits possess domain homology to subunits of the proteasome regulatory lid complex [5] [6]. Database searches indicate that only Sgn5/JAB1 is present in Saccharomyces cerevisiae, precluding genetic analysis of the complex in cell-cycle regulation. Here we identify a subunit of the signalosome in the fission yeast Schizosaccharomyces pombe through an analysis of the DNA-integrity checkpoint. We provide evidence for the conservation of the COP9/signalosome complex in fission yeast and demonstrate that it functions during S-phase progression.


Subject(s)
Plant Proteins/analysis , Plant Proteins/physiology , Proteins , S Phase/physiology , Schizosaccharomyces/chemistry , Schizosaccharomyces/cytology , Signal Transduction , COP9 Signalosome Complex , Cell Division , Cell Nucleus/metabolism , Checkpoint Kinase 1 , Conserved Sequence , DNA, Fungal/analysis , Genes, cdc , Humans , Immunoblotting , Microscopy, Fluorescence , Multiprotein Complexes , Mutagenesis , Peptide Hydrolases , Plants , Protein Kinases/genetics , Schizosaccharomyces/genetics
3.
Genes Dev ; 12(3): 382-95, 1998 Feb 01.
Article in English | MEDLINE | ID: mdl-9450932

ABSTRACT

Checkpoints that respond to DNA structure changes were originally defined by the inability of yeast mutants to prevent mitosis following DNA damage or S-phase arrest. Genetic analysis has subsequently identified subpathways of the DNA structure checkpoints, including the reversible arrest of DNA synthesis. Here, we show that the Cds1 kinase is required to slow S phase in the presence of DNA-damaging agents. Cds1 is phosphorylated and activated by S-phase arrest and activated by DNA damage during S phase, but not during G1 or G2. Activation of Cds1 during S phase is dependent on all six checkpoint Rad proteins, and Cds1 interacts both genetically and physically with Rad26. Unlike its Saccharomyces cerevisiae counterpart Rad53, Cds1 is not required for the mitotic arrest checkpoints and, thus, defines an S-phase specific subpathway of the checkpoint response. We propose a model for the DNA structure checkpoints that offers a new perspective on the function of the DNA structure checkpoint proteins. This model suggests that an intrinsic mechanism linking S phase and mitosis may function independently of the known checkpoint proteins.


Subject(s)
DNA Replication/physiology , Protein Kinases/metabolism , Protein Serine-Threonine Kinases , S Phase/physiology , Schizosaccharomyces pombe Proteins , Schizosaccharomyces/enzymology , Cell Cycle Proteins/genetics , Checkpoint Kinase 1 , Checkpoint Kinase 2 , DNA Damage/physiology , Enzyme Activation , Fungal Proteins/genetics , Fungal Proteins/physiology , Genes, Suppressor/genetics , Genes, Suppressor/physiology , Hydroxyurea/pharmacology , Mitosis/physiology , Molecular Sequence Data , Multigene Family/genetics , Multigene Family/physiology , Mutation/genetics , Mutation/physiology , Phosphoproteins/physiology , Phosphorylation , Protein Kinases/drug effects , Protein Kinases/genetics , Protein Kinases/physiology , Temperature
4.
Mol Gen Genet ; 255(2): 226-36, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9236781

ABSTRACT

In the fission yeast Schizosaccharomyces pombe, cells of opposite mating type communicate via diffusible peptide pheromones prior to mating. We have cloned the S. pombe mam1 gene, which encodes a 1336-amino acid protein belonging to the ATP-binding cassette (ABC) superfamily. The mam1 gene is only expressed in M cells and the gene product is responsible for the secretion of the mating pheromone. M-factor, a nonapeptide that is S-farnesylated and carboxy-methylated on its C-terminal cysteine residue. The predicted Mam1 protein is highly homologous to mammalian multiple drug-resistance proteins and to the Saccharomyces cerevisiae STE6 gene product, which mediates export of a-factor mating pheromone. We show that STE6 can also mediate secretion of M-factor in S. pombe.


Subject(s)
ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Glycoproteins , Guanine Nucleotide Exchange Factors , Peptides/metabolism , Saccharomyces cerevisiae Proteins , Schizosaccharomyces pombe Proteins , Schizosaccharomyces/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Amino Acid Sequence , Base Sequence , Cloning, Molecular , DNA-Binding Proteins , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Genetic Complementation Test , Intercellular Signaling Peptides and Proteins , Molecular Sequence Data , Mutation , Nitrogen/metabolism , Pheromones/metabolism , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Transcription, Genetic
6.
FEMS Microbiol Lett ; 147(1): 97-102, 1997 Feb 01.
Article in English | MEDLINE | ID: mdl-9037770

ABSTRACT

We have isolated the abc1 gene from the fission yeast Schizosaccharomyces pombe. Sequence analysis suggests that the Abc1 protein is a member of the ABC superfamily of transporters and is composed of two structurally homologous halves, each consisting of a hydrophobic region of six transmembrane domains and a hydrophilic region containing one ATP-binding site. The abc1 gene appears to be expressed under all growth conditions but gene disruption experiments indicate that it is not essential for growth. The sequence of the abc1 gene has been deposited in the EMBL data library under the Accession Number Y09354.


Subject(s)
Fungal Proteins/genetics , Schizosaccharomyces pombe Proteins , Schizosaccharomyces/chemistry , Schizosaccharomyces/genetics , ATP-Binding Cassette Transporters/genetics , DNA, Fungal/analysis , Genes, Fungal/genetics , Molecular Sequence Data , Mutagenesis/genetics , Schizosaccharomyces/metabolism , Sequence Analysis, DNA , Sequence Homology, Amino Acid
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