Sum1, a highly conserved WD-repeat protein, suppresses S-M checkpoint mutants and inhibits the osmotic stress cell cycle response in fission yeast.
The S-M checkpoint ensures that entry into mitosis is dependent on completion of DNA replication. In the fission yeast Schizosaccharomyces pombe, the SM checkpoint mutant cdc2-3w is thought to be defective in receiving the checkpoint signal. To isolate genes that function in the checkpoint pathway, we screened an S. pombe cDNA library for genes that, when overexpressed, could suppress the checkpoint defect of cdc2-3w. Using this approach, we have identified a novel gene, sum1+ (suppressor of uncontrolled mitosis). sum1+ encodes a highly conserved WD-transducin repeat protein with striking sequence similarity to the human transforming growth factor (TGF)-beta-receptor interacting protein TRIP-1 and to the translation initiation factor 3 subunit eIF3-p39, encoded by the TIF34 gene in Saccharomyces cerevisiae. S. pombe sum1+ is an essential gene, required for normal cell growth and division. In addition to restoring checkpoint control, overexpression of sum1+ inhibits the normal cell cycle response to osmotic stress. Furthermore, we demonstrate that inactivation of the stress-activated MAP kinase pathway, required for cell cycle stress response, restores the S-M checkpoint in cdc2-3w cells. These results suggest that Suml interacts with the stress-activated MAP kinase pathway and raise the possibility that environmental conditions may influence the checkpoint response in fission yeast.
Humphrey
T
T
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. t.humphrey@har.mrc.ac.uk
Enoch
T
T
D000595:Amino Acid Sequence; D001224:Aspartic Acid; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology; D017124:Conserved Sequence; D004271:DNA, Fungal / Q000096:biosynthesis; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006801:Humans; D020928:Mitogen-Activated Protein Kinases; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D009995:Osmosis; D051304:Profilins; D012568:Schizosaccharomyces / Q000235:genetics* / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins; D015293:Transducin / Q000737:chemistry; D014364:Tryptophan
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D051304:Profilins; C112648:SUM-1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C490133:cdc3 protein, S pombe; D001224:Aspartic Acid; D014364:Tryptophan; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016203:CDC2 Protein Kinase; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D015293:Transducin