Meiosis is a specialized cell cycle that generates recombinant, haploid progeny cells from a diploid cell. The meiotic cell cycle differs from the vegetative cell cycle in two outstanding respects. First, the S phase that occurs prior to meiosis (premeiotic S) is followed by two successive rounds of chromosome segregation, rather than alternating between S phase and mitosis. Second, the first meiotic division is reductional, resulting in the maintenance of cohesion between sister chromatids but the separation and segregation of homologous chromosomes. The preparation for this modified cell division cycle involves lengthy interaction between homologous chromosomes during the prophase stage of meiosis I but is likely to initiate as early as premeiotic S phase. Premeiotic S phase is longer than S phase in vegetative cells in most organisms. The cause of this difference is unclear, since experiments in budding yeast suggest that the same replication origins are active in vegetative and meiotic cells. However, other experiments in S. cerevisiae suggest that meiosis-specific chromosomal factors required during prophase might assemble during premitotic STET.
Recent studies in Saccharomyces pombe have addressed the question of whether the replication machinery that functions during premeiotic S phase is the same as that utilized in the vegetative cell cycle. S. pombe proteins required for the actual synthesis of the DNA in vegetative cells, such as DNA polymerase α and ribonucleotide reductase, also are essential for premeiotic S phase. In contrast, mutants defective in initiation of DNA replication, such as the mcm mutants and cdc18, display different phenotypes in meiosis and mitosis. In mitosis, conditional alleles of these mutants allow bulk DNA replication but cause cells to arrest in late S phase. In contrast, in similar conditions these mutants can proceed through the meiotic divisions and sporulate. With more extreme conditions, these mutants delay replication and the subsequent meiotic divisions. This may reflect a quantitative difference: meiotic cells may tolerate a lower amount of certain replication proteins than that needed during the vegetative cell cycle. It is also possible that other meiotic factors, perhaps recombination proteins, can contribute to premeiotic replication.
The S. pombe MCM protein complex is associated with chromatin during premeiotic S phase, consistent with the hypothesis that these proteins function in premeiotic DNA replication. However, MCM proteins are not localized to chromatin in between the meiotic divisions, when an additional round of DNA replication is suppressed. Similar to the vegetative cell cycle, the meiotic cell cycle is subject to checkpoint controls. Fission yeast cells that have been induced to enter meiosis block the cell cycle when treated with HU. As in the vegetative cell cycle, HU-induced arrest during meiosis is likely to be checkpoint-dependent. Future work should resolve the components of this response, which are likely to be essential for the viability of gametes. Importantly, premeiotic S phase is closely coupled to the downstream events of meiosis such as recombination. This has been best demonstrated in budding yeast, where blocks to premeiotic DNA synthesis prevent meiotic recombination and changes in the timing of premeiotic replication result in corresponding changes in the timing of initiation of meiotic recombination. The molecular mechanism by which this occurs is still unclear.
