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

Abstract

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 phase1,2,3,4,5, leading to the view that initiation of recombination depends on meiotic DNA replication6,7. 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 meiosis8. We have investigated these possibilities in the fission yeast Schizosaccharomyces pombe and found that core DNA replication initiation proteins used during the mitotic cell cycle9,10, 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.

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Figure 1: DNA replication initiation proteins are required for premeiotic DNA replication.
Figure 2: Cdc18p is expressed during meiosis and is required for premeiotic DNA replication.
Figure 3: DNA replication initiation proteins are not required for meiotic DSBs.
Figure 4: Meiotic DSBs occur independently of the completion of premeiotic DNA replication.

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Acknowledgements

We are grateful to G. Smith, T. Kelly and H. Nishitani for strains, plasmids and antibodies. We thank J. Hayles, J. Bähler, T. Toda and S. Yanow for critical reading of the manuscript and M. Lichten and A. Nicolas for helpful comments on the manuscript and for communicating unpublished results. We thank all members of the cell cycle laboratory for their help. H.M. was supported by The Japanese Society for the Promotion of Science and the Imperial Cancer Research Fund.

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Correspondence to Hiroshi Murakami.

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Murakami, H., Nurse, P. Regulation of premeiotic S phase and recombination-related double-strand DNA breaks during meiosis in fission yeast. Nat Genet 28, 290–293 (2001). https://doi.org/10.1038/90142

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