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 ind uced by DNA double-strand breaks (DSBs). which appear after completion of p remeiotic S phase(1-5), leading to the view that initiation of recombinatio n depends on meiotic DNA replication(6,7). It has also been indicated that DNA replication initiation proteins may differ between the meiotic and mito tic 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 foun d that core DNA replication initiation proteins used during the mitotic cel l cycle(9,0), including Cdc18p (budding yeast Cdc6p), Cdc19p (Mcm2p), Cdc21 p (Mcm4p) and Orp1p (Orc1p), are also required for premeiotic S phase. Redu ced activity of these proteins prevents completion of DNA replication but n ot 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 fo r premeiotic S phase and the other for initiating recombination.