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 <i>Schizosaccharomyces pombe</i> has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in <i>S. pombe</i> ‘cut’ (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of <i>cbf11</i>, 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 <i>cut6</i>, and the biotin uptake/biosynthesis genes <i>vht1</i> and <i>bio2</i>, with the former 2 implicated in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response element (GTGGGAA) in the <i>cut6</i> promoter. Expression of Cbf11 target genes shows apparent oscillations during the cell cycle using temperature-sensitive <i>cdc25–22</i> and <i>cdc10-M17</i> block-release experiments, but not with other synchronization methods. The penetrance of catastrophic mitosis in <i>cbf11</i> and <i>cut6</i> 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.