The CLN3/SWI6/CLN2 pathway and SNF1 act sequentially to regulate meiotic initiation in Saccharomyces cerevisiae

Abstract

Background: IME1, which is required for the initiation of meiosis, is regulated by Cln3:Cdc28 kinase, which activates the G1‐to‐S transition, and Snf1 kinase, which mediates glucose repression. Here we examine the pathway by which Cln3:Cdc28p represses IME1 and the relationship between Cln3:Cdc28p and Snf1p in this regulation. Results: When wild‐type yeast cease growth, they express IME1 to moderate levels, intermediate between the low levels expressed during growth and the high levels expressed during sporulation. Moderate IME1 expression occurred in cln3Δ, cln1Δ cln2Δ, cdc28‐4 and swi6Δ mutants, even during growth. These mutants also induced IME1 expression more rapidly than the wild‐type. CLN3 required SWI6 and CLN2 to repress IME1 and IME2, but CLN1 was much less active than CLN2 in this repression. The phenotype of the cln3Δ snf1Δ double mutant indicated that Cln3:Cdc28p regulates IME1 independently of SNF1. Conclusion: Entry into meiosis involves two independent but sequential controls, which regulate IME1 via a three position switch: (i) during growth IME1 is repressed by the CLN3/SWI6/CLN2 pathway, (ii) once growth ceases, this repression is released and IME1 is expressed at moderate levels, and (iii) subsequently, nutritional conditions that activate Snf1p allow high IME1 expression.

Glucose Inhibits Meiotic DNA Replication through SCFGrr1p-Dependent Destruction of Ime2p Kinase

“…We propose that moderate concentrations of glucose present during late stages of growth block meiotic DNA replication via the Grr1p/Ime2p/Sic1p pathway without preventing moderate expression of IME1 and IME2. This moderate expression of IME1 and IME2 during late stages of growth may explain why these cultures can initiate meiosis much faster than mid-log cultures (39).…”

Execution of the meiotic noncoding RNA expression program and the onset of gametogenesis in yeast require the conserved exosome subunit Rrp6

“…In such a case, it is not the ncRNA itself but its synthesis and the pausing of RNA polymerase during elongation that prevents activator binding (35). For example, the mRNA concentration of CLN2 declines during sporulation, and its 5′-regulatory region is covered by MUT1465; CLN2 is a repressor of IME1 (the inducer of meiosis), and therefore CLN2's down-regulation is important for the onset of meiosis (36). Another interesting example is CDC6, which is essential for DNA replication (37).…”

Molecular basis of the functional distinction between Cln1 and Cln2 cyclins

“…Thus, Cln1 is more important than Cln2 in adapting cell size to new carbon sources 36 and pseudohyphal development, 37,38 but these functional distinctions seem to be caused by quantitative differences in gene expression. On the other hand, meiosis is blocked more efficiently in the presence of Cln2 than in Cln1, 39 and Cln2 plays the primary role in the morphogenetic processes leading to budding during the G 1 /S transition. 40 More recently, cyclin-specific docking motifs that bind preferentially to Cln2 have been described in signaling proteins, such as Ste5 and Ste20.…”