The sak1+ gene of Schizosaccharomyces pombe encodes an RFX family DNA-binding protein that positively regulates cyclic AMP-dependent protein kinase-mediated exit from the mitotic cell cycle.
In Schizosaccharomyces pombe, meiosis is initiated by conditions of nutrient deprivation. Mutations in genes encoding elements of the cyclic AMP-dependent protein kinase (cAPK) pathway interfere with meiosis. Loss-of-function alleles of genes that stimulate the activity of cAPK allow cells to bypass the normal requirement of starvation for conjugation and meiosis. Alternatively, loss-of-function alleles of genes that inhibit cAPK lead to the inability to undergo sexual differentiation. The cgs1+ gene encodes the regulatory subunit of cAPK, and the cgs2+ gene encodes a cyclic AMP phosphodiesterase. Thus, both genes encode proteins which negatively regulate the activity of cAPK. Loss of either cgs1 or cgs2 prevents haploid cells from conjugating and diploid cells from undergoing meiosis. In addition to these defects, cells are unable to enter stationary phase. We describe a novel gene, sak1+, which when present on a plasmid overcomes the aberrant phenotypes associated with unregulated cAPK activity. Genetic analysis of sak1+ (suppressor of A-kinase) reveals that it functions downstream of cyclic AMP-dependent protein kinase to allow cells to exist the mitotic cycle and enter either stationary phase or the pathway leading to sexual differentiation. The sak1+ gene is essential for cell viability, and a null allele causes multiple defects in cell morphology and nuclear division. Thus, sak1+ is an important regulatory element in the life cycle of S. pombe. Sequence analysis shows that the predicted product of the sak1+ gene is an 87-kDa protein which shares homology to the RFX family of DNA-binding proteins identified in humans and mice. One member of this family, RFX1, is a transcription factor for a variety of viral and cellular genes.
Wu
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SY
State University of New York Health Science Center at Brooklyn, 11203.
McLeod
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D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D005838:Genotype; D006706:Homeostasis; D008540:Meiosis; D008938:Mitosis; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010641:Phenotype; D010957:Plasmids; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; D012045:Regulatory Sequences, Nucleic Acid; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; C000605537:RFX1 protein, human; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; C000605538:Rfx1 protein, mouse; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C092118:sak1 protein, S pombe; D017868:Cyclic AMP-Dependent Protein Kinases