Regulation of premeiotic S phase and recombination-related double-strand DNA breaks during meiosis in fission yeast

The meiotic cell cycle is characterized by high levels of recombination induced by DNA double-strand breaks (DSBs). which appear after completion of premeiotic S phase(1-5), leading to the view that initiation of recombination depends on meiotic DNA replication(6,7). It has also been indicated that DNA replication initiation proteins may differ between the meiotic and mitotic cell cycles, giving rise to an altered S phase, which could contribute to the high level of recombination during meiosis(8). We have investigated these possibilities in the fission yeast Schizosaccharomyces pombe and found that core DNA replication initiation proteins used during the mitotic cell cycle(9,0), including Cdc18p (budding yeast Cdc6p), Cdc19p (Mcm2p), Cdc21p (Mcm4p) and Orp1p (Orc1p), are also required for premeiotic S phase. Reduced activity of these proteins prevents completion of DNA replication but not formation of DSBs. We conclude that recombination-related DSB formation does not depend on the completion of meiotic DNA replication and we propose two parallel developmental sequences during the meiotic cell cycle: one for premeiotic S phase and the other for initiating recombination.