Abstract
BackgroundIn Saccharomyces cerevisiae, the G1 cyclin/cyclin-dependent kinase (CDK) complexes Cln1,-2,-3/Cdk1 promote S phase entry during the mitotic cell cycle but do not function during meiosis. It has been proposed that the meiosis-specific protein kinase Ime2, which is required for normal timing of pre-meiotic DNA replication, is equivalent to Cln1,-2/Cdk1. These two CDK complexes directly catalyze phosphorylation of the B-type cyclin/CDK inhibitor Sic1 during the cell cycle to enable its destruction. As a result, Clb5,-6/Cdk1 become activated and facilitate initiation of DNA replication. While Ime2 is required for Sic1 destruction during meiosis, evidence now suggests that Ime2 does not directly catalyze Sic1 phosphorylation to target it for destabilization as Cln1,-2/Cdk1 do during the cell cycle.Methodology/Principal FindingsWe demonstrated that Sic1 is eventually degraded in meiotic cells lacking the IME2 gene (ime2Δ), supporting an indirect role of Ime2 in Sic1 destruction. We further examined global RNA expression comparing wild type and ime2Δ cells. Analysis of these expression data has provided evidence that Ime2 is required early in meiosis for normal transcription of many genes that are also periodically expressed during late G1 of the cell cycle.Conclusions/SignificanceOur results place Ime2 at a position in the early meiotic pathway that lies upstream of the position occupied by Cln1,-2/Cdk1 in the analogous cell cycle pathway. Thus, Ime2 may functionally resemble Cln3/Cdk1 in promoting S phase entry, or it could play a role even further upstream in the corresponding meiotic cascade.
Highlights
Gametogenesis includes the specialized process of meiosis whereby haploid cells are generated from diploid precursors
Sic1 level decreases in ime2D cells In wild type (WT) cells undergoing meiosis, Ime2 is required for the timely destruction of the B-type cyclin/cyclin-dependent kinase (CDK) inhibitor Sic1, which leads to initiation of pre-meiotic DNA replication [3,29]
To determine whether Sic1 is eventually degraded in ime2D cells to allow for delayed initiation of DNA replication, as has been suggested previously [36], we examined the behavior of epitope-tagged Sic1 (Sic113myc) in WT and ime2D cells that were induced to enter meiosis synchronously
Summary
Gametogenesis includes the specialized process of meiosis whereby haploid cells are generated from diploid precursors. The budding yeast Saccharomyces cerevisiae has been an invaluable model for characterizing fundamental cell cycle processes, including those that govern S phase entry. This system has contributed greatly to our understanding of meiosis, which is linked to sporulation in S. cerevisiae. In Saccharomyces cerevisiae, the G1 cyclin/cyclin-dependent kinase (CDK) complexes Cln1,-2,-3/Cdk promote S phase entry during the mitotic cell cycle but do not function during meiosis. It has been proposed that the meiosisspecific protein kinase Ime, which is required for normal timing of pre-meiotic DNA replication, is equivalent to Cln1,-2/ Cdk1 These two CDK complexes directly catalyze phosphorylation of the B-type cyclin/CDK inhibitor Sic during the cell cycle to enable its destruction. While Ime is required for Sic destruction during meiosis, evidence suggests that Ime does not directly catalyze Sic phosphorylation to target it for destabilization as Cln1,-2/Cdk do during the cell cycle
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