Fission yeast APC/C activators Slp1 and Fzr1 sequentially trigger two consecutive nuclear divisions during meiosis

Abstract

In meiosis, two rounds of nuclear division occur consecutively without DNA replication between the divisions. We isolated a fission yeast mutant in which the nucleus divides only once to generate two spores, as opposed to four, in meiosis. In this mutant, we found that the initiation codon of the slp1 gene is converted to ATA, producing a reduced amount of Slp1. As a member of the Fizzy family of anaphase-promoting complex/cyclosome (APC/C) activators, Slp1 is essential for vegetative growth; however, the mutant allele shows a phenotype only in meiosis. Slp1 insufficiency delays degradation of maturation-promoting factor at the first meiotic division, and another APC/C activator, Fzr1, which acts late in meiosis, terminates meiosis immediately after the delayed first division to produce two viable spores.

CDK Regulation of Meiosis: Lessons from S. cerevisiae and S. pombe

“…Fourth, the cyclins are ubiquitinated and targeted for proteasomal degradation in anaphase I and anaphase II by the APC/C ubiquitin ligase. In meiosis, the APC/C mainly uses two co-activators, Slp1 (Cdc20 in budding yeast) and a meiosis-specific co-activator Mfr1/Fzr1 [ 184 , 185 , 186 , 187 ] ( Table 1 ).…”

“…There is a precise balance in maintaining the correct levels of Cdc13 between the meiotic divisions ( Figure 2 ). In mes1Δ mutants, Cdc13 is completely degraded and cells cannot progress into meiosis II [ 187 , 244 , 245 , 246 ]. A loss of fzr1 allows mes1Δ cells to undergo meiosis II, demonstrating that reducing APC/C activity is important for the transition to meiosis II [ 186 , 187 , 246 ].…”

“…In anaphase I, CDK activity must be downregulated to allow spindle disassembly and meiosis I exit. In both budding and fission yeast, APC/C-Cdc20/Slp1 becomes active to target both securin and the cyclins for degradation at the metaphase I-to-anaphase I transition [ 67 , 187 ]. In budding yeast, some of the cyclins are post-translationally regulated for inactivation [ 51 ].…”

“…Both the decline in CDK activity and the release of the Cdc14 phosphatase is needed for spindle disassembly [ 62 , 63 ]. In fission yeast, APC/C-Slp1 targets securin and Cdc13 for degradation at the metaphase I-to-anaphase I transition [ 187 , 246 ]. The Cdc14-like phosphatase Clp1 is not needed for normal meiotic timings or spindle disassembly, but may help with the fidelity of the process [ 35 ].…”

“…The Cdc14 phosphatase is released from the nucleolus and removes phosphorylation from CDK substrates [ 62 , 63 , 253 ]. In fission yeast, APC/C-Slp1 and APC/C-Fzr1 target cyclins for degradation [ 184 , 185 , 186 , 187 , 246 ]. Clp1 likely reverses the phosphorylation of CDK substrates.…”