CSL protein regulates transcription of genes required to prevent catastrophic mitosis in fission yeast.
For every eukaryotic cell to grow and divide, intricately coordinated action of numerous proteins is required to ensure proper cell-cycle progression. The fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL transcription factor gene, triggers a 'cut' phenotype, but the precise role of Cbf11 in promoting mitotic fidelity is not known. We report that Cbf11 directly activates the transcription of the acetyl-coenzyme A carboxylase gene cut6, and the biotin uptake/biosynthesis genes vht1 and bio2, with the former 2 implicated in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response element (GTGGGAA) in the cut6 promoter. Expression of Cbf11 target genes shows apparent oscillations during the cell cycle using temperature-sensitive cdc25-22 and cdc10-M17 block-release experiments, but not with other synchronization methods. The penetrance of catastrophic mitosis in cbf11 and cut6 mutants is nutrient-dependent. We also show that drastic decrease in biotin availability arrests cell proliferation but does not cause mitotic defects. Taken together, our results raise the possibility that CSL proteins play conserved roles in regulating cell-cycle progression, and they could guide experiments into mitotic CSL functions in mammals.
a Department of Cell Biology , Faculty of Science, Charles University in Prague , Prague , Czech Republic.
Martin
M
Převorovský
a Department of Cell Biology , Faculty of Science, Charles University in Prague , Prague , Czech Republic.
Martina
M
Oravcová
a Department of Cell Biology , Faculty of Science, Charles University in Prague , Prague , Czech Republic.
Róbert
R
Zach
a Department of Cell Biology , Faculty of Science, Charles University in Prague , Prague , Czech Republic.
Anna
A
Jordáková
b Research Department of Genetics , Evolution & Environment and UCL Cancer Institute, University College London , Gower Street, London , UK.
Jürg
J
Bähler
a Department of Cell Biology , Faculty of Science, Charles University in Prague , Prague , Czech Republic.
František
F
Půta
a Department of Cell Biology , Faculty of Science, Charles University in Prague , Prague , Czech Republic.
Petr
P
Folk
D001710:Biotin / Q000378:metabolism; D004271:DNA, Fungal / Q000378:metabolism; D004843:Epistasis, Genetic; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008938:Mitosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004271:DNA, Fungal; D029702:Schizosaccharomyces pombe Proteins; D001710:Biotin
Schizosaccharomyces pombe; biotin; catastrophic mitosis; cut; periodic gene expression; premature cytokinesis; transcription factor
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