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Fission yeast Mes1p ensures the onset of meiosis II by blocking degradation of cyclin Cdc13p

Nature volume 434, pages 529–533 (2005)Cite this article

Abstract

Meiosis is a special form of nuclear division to generate eggs, sperm and spores in eukaryotes. Meiosis consists of the first (MI) and the second (MII) meiotic divisions, which occur consecutively. MI is reductional, in which homologous chromosomes derived from parents segregate. MI is supported by an elaborate mechanism involving meiosis-specific cohesin and its protector1. MII is equational, in which replicated sister-chromatids separate as in mitosis. MII is generally considered to mimic mitosis in mechanism. However, fission yeast Mes1p is essential for MII but dispensable for mitosis. The mes1-B44 mutant arrests before MII2. Transcription of mes1 is low in vegetative cells and boosted in a narrow window between late MI and late MII3. The mes1 mRNA undergoes meiosis-specific splicing4. Here we show that Mes1p is a factor that suppresses the degradation of cyclin Cdc13p at anaphase I. Mes1p binds to Slp1p, an activator of APC/C (anaphase promoting complex/cyclosome), and counteracts its function to engage Cdc13p in proteolysis. Inhibition of APC/C-dependent degradation of Cdc13p by Mes1p was reproduced in a Xenopus egg extract. We therefore propose that Mes1p has a key function in saving a sufficient level of MPF (M-phase-promoting factor) activity required for the execution of MII.

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Figure 1: Mes1p is required to maintain MPF activity after MI.
Figure 2: Interaction of Mes1p with Slp1p, which recruits Cdc13p to proteolysis.
Figure 3: Mes1p inhibits the function of Slp1p in activating APC/C.
Figure 4: Mes1p blocks Slp1p-APC/C function to degrade Cdc13p.

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References

  1. Watanabe, Y. Modifying sister chromatid cohesion for meiosis. J. Cell Sci. 117, 4017–4023 (2004)

    Article  CAS  Google Scholar 

  2. Shimoda, C., Hirata, A., Kishida, M., Hashida, T. & Tanaka, K. Characterization of meiosis-deficient mutants by electron microscopy and mapping of four essential genes in the fission yeast Schizosaccharomyces pombe. Mol. Gen. Genet. 200, 252–257 (1985)

    Article  CAS  Google Scholar 

  3. Mata, J., Lyne, R., Burns, G. & Bahler, J. The transcriptional program of meiosis and sporulation in fission yeast. Nature Genet. 32, 143–147 (2002)

    Article  CAS  Google Scholar 

  4. Kishida, M., Nagai, T., Nakaseko, Y. & Shimoda, C. Meiosis-dependent mRNA splicing of the fission yeast Schizosaccharomyces pombe mes1+ gene. Curr. Genet. 25, 497–503 (1994)

    Article  CAS  Google Scholar 

  5. Decottignies, A., Zarzov, P. & Nurse, P. In vivo localisation of fission yeast cyclin-dependent kinase cdc2p and cyclin B cdc13p during mitosis and meiosis. J. Cell Sci. 114, 2627–2640 (2001)

    CAS  PubMed  Google Scholar 

  6. Borgne, A., Murakami, H., Ayte, J. & Nurse, P. The G1/S cyclin Cig2p during meiosis in fission yeast. Mol. Biol. Cell 13, 2080–2090 (2002)

    Article  CAS  Google Scholar 

  7. Gould, K. L. & Nurse, P. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature 342, 39–45 (1989)

    Article  ADS  CAS  Google Scholar 

  8. Bueno, A. & Russell, P. Two fission yeast B-type cyclins, cig2 and cdc13, have different functions in mitosis. Mol. Cell. Biol. 13, 2286–2297 (1993)

    Article  CAS  Google Scholar 

  9. Matsumoto, T. A fission yeast homolog of CDC20/p55CDC/Fizzy is required for recovery from DNA damage and genetically interacts with p34cdc2. Mol. Cell. Biol. 17, 742–750 (1997)

    Article  CAS  Google Scholar 

  10. Visintin, R., Prinz, S. & Amon, A. CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science 278, 460–463 (1997)

    Article  ADS  CAS  Google Scholar 

  11. Fang, G., Yu, H. & Kirschner, M. W. Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. Mol. Cell 2, 163–171 (1998)

    Article  CAS  Google Scholar 

  12. Peters, J. M. The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol. Cell 9, 931–943 (2002)

    Article  CAS  Google Scholar 

  13. Burton, J. L. & Solomon, M. J. D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p. Genes Dev. 15, 2381–2395 (2001)

    Article  CAS  Google Scholar 

  14. Yamada, H. Y., Matsumoto, S. & Matsumoto, T. High dosage expression of a zinc finger protein, Grt1, suppresses a mutant of fission yeast slp1+, a homolog of CDC20/p55CDC/Fizzy. J. Cell Sci. 113, 3989–3999 (2000)

    CAS  PubMed  Google Scholar 

  15. Funabiki, H. et al. Cut2 proteolysis required for sister-chromatid seperation in fission yeast. Nature 381, 438–441 (1996)

    Article  ADS  CAS  Google Scholar 

  16. He, X., Patterson, T. E. & Sazer, S. The Schizosaccharomyces pombe spindle checkpoint protein mad2p blocks anaphase and genetically interacts with the anaphase-promoting complex. Proc. Natl Acad. Sci. USA 94, 7965–7970 (1997)

    Article  ADS  CAS  Google Scholar 

  17. Moreno, S., Hayles, J. & Nurse, P. Regulation of p34cdc2 protein kinase during mitosis. Cell 58, 361–372 (1989)

    Article  CAS  Google Scholar 

  18. Blanco, M. A., Pelloquin, L. & Moreno, S. Fission yeast mfr1 activates APC and coordinates meiotic nuclear division with sporulation. J. Cell Sci. 114, 2135–2143 (2001)

    CAS  PubMed  Google Scholar 

  19. Yamano, H., Gannon, J., Mahbubani, H. & Hunt, T. Cell cycle-regulated recognition of the destruction box of cyclin B by the APC/C in Xenopus egg extracts. Mol. Cell 13, 137–147 (2004)

    Article  CAS  Google Scholar 

  20. Yamano, H. et al. The spike of S phase cyclin Cig2 expression at the G1-S border in fission yeast requires both APC and SCF ubiquitin ligases. Mol. Cell 6, 1377–1387 (2000)

    Article  CAS  Google Scholar 

  21. Nakajo, N. et al. Absence of Wee1 ensures the meiotic cell cycle in Xenopus oocytes. Genes Dev. 14, 328–338 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Iwabuchi, M., Ohsumi, K., Yamamoto, T. M., Sawada, W. & Kishimoto, T. Residual Cdc2 activity remaining at meiosis I exit is essential for meiotic M-M transition in Xenopus oocyte extracts. EMBO J. 19, 4513–4523 (2000)

    Article  CAS  Google Scholar 

  23. Kim, S. H., Lin, D. P., Matsumoto, S., Kitazono, A. & Matsumoto, T. Fission yeast Slp1: an effector of the Mad2-dependent spindle checkpoint. Science 279, 1045–1047 (1998)

    Article  ADS  CAS  Google Scholar 

  24. Shah, J. V. & Cleveland, D. W. Waiting for anaphase: Mad2 and the spindle assembly checkpoint. Cell 103, 997–1000 (2000)

    Article  CAS  Google Scholar 

  25. Reimann, J. D. et al. Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Cell 105, 645–655 (2001)

    Article  CAS  Google Scholar 

  26. Reimann, J. D. & Jackson, P. K. Emi1 is required for cytostatic factor arrest in vertebrate eggs. Nature 416, 850–854 (2002)

    Article  ADS  CAS  Google Scholar 

  27. Ohsumi, K., Koyanagi, A., Yamamoto, T. M., Gotoh, T. & Kishimoto, T. Emi1-mediated M-phase arrest in Xenopus eggs is distinct from cytostatic factor arrest. Proc. Natl Acad. Sci. USA 101, 12531–12536 (2004)

    Article  ADS  CAS  Google Scholar 

  28. Reimann, J. D., Gardner, B. E., Margottin-Goguet, F. & Jackson, P. K. Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins. Genes Dev. 15, 3278–3285 (2001)

    Article  CAS  Google Scholar 

  29. Moreno, S., Klar, A. & Nurse, P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 194, 795–823 (1991)

    Article  CAS  Google Scholar 

  30. Maundrell, K. nmt1 of fission yeast. A highly transcribed gene completely repressed by thiamine. J. Biol. Chem. 265, 10857–10864 (1990)

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank K. Tsumoto and M. Toya for technical assistance, Y. Watanabe and Y. Imai for helpful discussion, M. Yanagida for anti-Cut2p antibodies, and T. Matsumoto for the slp1-362 strain. This work was supported by a Grant-in-Aid for Specially Promoted Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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  1. Masuo Goto

    Present address: NIEHS, NIH, Research Triangle Park, North Carolina, 27709-2233, USA

Authors and Affiliations

  1. Department of Biophysics and Biochemistry, Graduate School of Science,

    Daisuke Izawa & Masayuki Yamamoto

  2. Molecular Genetics Research Laboratory, University of Tokyo, Tokyo, Hongo, 113-0033, Japan

    Akira Yamashita & Masayuki Yamamoto

  3. Division of Cell Proliferation, National Institute for Basic Biology, Okazaki, Aichi, 444-0867, Japan

    Masuo Goto

  4. Cell Cycle Control Group, Marie Curie Research Institute, The Chart, Oxted, Surrey, RH8 0TL, UK

    Hiroyuki Yamano

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Correspondence to Masayuki Yamamoto.

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Izawa, D., Goto, M., Yamashita, A. et al. Fission yeast Mes1p ensures the onset of meiosis II by blocking degradation of cyclin Cdc13p. Nature 434, 529–533 (2005). https://doi.org/10.1038/nature03406

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