| It is well established that commitment to mitosis is dependent upon the attainment of a minimum cell size which is intimately dependent upon Clns and the activity of Cln:Cdc28 kinases[1-3]. While Clns are required for mitotic cell cycle progression, they are not required for meiosis [4]. This suggests that the mechanism that cells use to switch from mitotic proliferation to meiotic differentiation is sensitive to Cln:Cdc28 activity. The relationship between Cln:Cdc28 activity, cell size, and meiosis is not known. Because Cln:Cdc28 activity influences both cell size and meiosis, it has remained difficult to establish how cell size, in the absence of Cln:Cdc28 activity, affects initiation of meiosis.;We hypothesized that there is a cell size threshold for meiosis which is dependent upon Cln:Cdc28 kinase activity. We found that the meiotic size initiation threshold (MIST) could be bypassed in the absence of Clns, or the presence of a temperature sensitive CDC28 mutation. Therefore, we concluded that Cln:Cdc28 kinase complexes inhibit initiation of meiosis predominately through a cell size-dependent mechanism.;In yeast, initiation of meiosis relies upon the activation of a cascade of meiotic-specific gene transcripts induced by the Ime1 transcription factor [5-7]. Because Clns influence cell size and affect IME1 expression[4, 8] we questioned if cell size could alter Ime1 expression or activity. We found that Ime1 RNA and protein expression was unaffected by cell size but Ime1 transcriptional activity was repressed in a size dependent manner. This repression is partially due to the inability of Ime1 to enter the nucleus of cells below the required size threshold.;The S-phase cyclins Clb5 and Clb6 are dispensable for mitosis but required for meiosis. We sought to establish if there was any variability in S-phase cyclin abundance related to cell size. These experiments showed that S-phase cyclin gene/protein expression was dependent upon achievement of a prerequisite cell size. These results support a model whereby pre-meiotic DNA replication is blocked due to loss of S-phase cyclin expression in cells below MIST. Overall, this study identified multiple cell size related factors which play important roles in regulating the switch between mitosis and meiosis.;1Cross, F.R., Starting the cell cycle: what's the point? Curr Opin Cell Biol, 1995. 7(6): p. 790-7. 2Futcher, B., Cyclins and the wiring of the yeast cell cycle. Yeast, 1996. 12(16): p. 1635-46. 3Nasmyth, K., Control of the yeast cell cycle by the Cdc28 protein kinase. Curr Opin Cell Biol, 1993. 5(2): p. 166-79. 4Colomina, N., et al., G1 cyclins block the Ime1 pathway to make mitosis and meiosis incompatible in budding yeast. Embo J, 1999. 18(2): p. 320-9. 5Kupiec, M., Byers, B., Esposito, R.E., and Mitchelle A.P., Meiosis and Sporulation in Saccaromyces cerevisiae, in Yeast III. 1997, Cold Spring Harbor Laboratory Press. p. 889-1036. 6Honigberg, S.M. and K. Purnapatre, Signal pathway integration in the switch from the mitotic cell cycle to meiosis in yeast. J Cell Sci, 2003. 116(Pt 11): p. 2137-47. 7Kassir, Y., et al., Transcriptional regulation of meiosis in budding yeast. Int Rev Cytol, 2003. 224: p. 111-71. 8Purnapatre, K., et al., The CLN3/SWI6/CLN2 pathway and SNF1 act sequentially to regulate meiotic initiation in Saccharomyces cerevisiae. Genes Cells, 2002. 7(7): p. 675-91. |
