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MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells

Abstract

AN intact nuclear membrane restricts DNA replication to only one round in each cell cycle, apparently by excluding an essential replication-licensing factor throughout interphase1–5. A family of related yeast replication proteins, MCM2, 3 and 5 (also called, after cell-division cycle, CDC46), resemble licensing factor, entering the nucleus only during mitosis6–8. We have cloned a Xenopus homologue of MCM3 (XMCM3) and raised antibodies against expressed protein. Immunodepletion of Xenopus egg extracts removes a complex of MCM2, 3 and 5 homologues and inhibits replication of Xenopus sperm nuclei or permeable G2 HeLa nuclei. However, Gl HeLa nuclei still replicate efficiently. Mock-depleted extracts replicate all three templates. XMCM3 accumulates in nuclei before replication but anti-XMCM3 staining decreases during replication. These results can explain why replicated nuclei are unable to reinitiate replication in a single cell cycle.

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References

  1. Blow, J. J. & Laskey, R. A. Nature 332, 546–548 (1988).

    Article  ADS  CAS  Google Scholar 

  2. Leno, G. H., Downes, C. S. & Laskey, R. A. Cell 69, 151–158 (1992).

    Article  CAS  Google Scholar 

  3. Coverley, D., Downes, C. S., Romanowski, P. & Laskey, R. A. J. Cell Biol. 122, 985–992 (1993).

    Article  CAS  Google Scholar 

  4. Blow, J. J. J. Cell Biol. 122, 993–1002 (1993).

    Article  CAS  Google Scholar 

  5. Kubota, Y. & Takisawa, H. J. Cell Biol. 123, 1321–1331 (1993).

    Article  CAS  Google Scholar 

  6. Hennessy, K. M., Clark, C. D. & Botstein, D. Genes Dev. 4, 2252–2263 (1990).

    Article  CAS  Google Scholar 

  7. Yan, H., Merchant, A. M. & Tye, B. K. Genes Dev. 7, 2149–2160 (1993).

    Article  CAS  Google Scholar 

  8. Tye, B.-K. Trends Cell Biol. 4, 160–166 (1994).

    Article  CAS  Google Scholar 

  9. Yan, H., Gibson, S. & Tye, B.-K. Genes Dev. 5, 944–957 (1991).

    Article  CAS  Google Scholar 

  10. Thömmes, P. et al. Nucleic. Acids Res. 20, 1069–1074 (1992).

    Article  Google Scholar 

  11. Todorov, I. T. et al. J. Cell Sci. 107, 253–265 (1994).

    CAS  PubMed  Google Scholar 

  12. Hu, B., Burkhart, R., Schulte, D., Musahl, C. & Knippers, R. Nucleic Acids Res. 21, 5289–5293 (1993).

    Article  CAS  Google Scholar 

  13. Chong, J. P. J., Mahbubani, H. M., Khoo, C.-Y. & Blow, J. J. Nature 375, 418–421 (1995).

    Article  ADS  CAS  Google Scholar 

  14. Burkhart, R. et al. Eur J. Biochem. 228, 431–438 (1995).

    Article  CAS  Google Scholar 

  15. Gibson, S. I., Surosky, R. T. & Tye, B. K. Molec. cell. Biol. 10, 5707–5720 (1990).

    Article  CAS  Google Scholar 

  16. Hennesy, K. M., Lee, A., Chen, E. & Botstein, D. Genes Dev. 5, 958–969 (1991).

    Article  Google Scholar 

  17. Kimura, H., Nozaki, N. & Sugimoto, K. EMBO J. 13, 4311–4320 (1994).

    Article  CAS  Google Scholar 

  18. Rao, P. N. & Johnson, R. T. Nature 225, 159–164 (1970).

    Article  ADS  CAS  Google Scholar 

  19. Kubota, Y., Mimura, S., Nishimoto, S., Takisawa, H. & Nojima, H. Cell (in press 1995).

  20. Görlich, D., Prehn, S., Laskey, R. A. & Hartmann, E. Cell 79, 767–778 (1994).

    Article  Google Scholar 

  21. Bucci, S. et al. Int. J. devl Biol. 37, 509–517 (1993).

    CAS  Google Scholar 

  22. Lemaire, P., Garrett, N.,. Kato, K. & Gurdon, J. B. C. R. Acad. Sci., Paris 316, 938–944 (1993).

    Google Scholar 

  23. Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, New York, 1991).

    Google Scholar 

  24. Devereux, J., Haeberlin, P. & Smithies, O. Nucleic Acids Res. 12, 387–395 (1984).

    Article  CAS  Google Scholar 

  25. Nagai, K. & Thøgersen, H. C. Method. Enzym. 153, 461–481 (1987).

    Article  CAS  Google Scholar 

  26. Harlow, E. & Lane, D. Antibodies: A Laboratory Manual (Cold Spring Harbor Lab. Press, New York, 1988).

    Google Scholar 

  27. Blow, J. J. & Laskey, R. A. Cell 47, 577–587 (1986).

    Article  CAS  Google Scholar 

  28. Sheehan, M. A., Mills, A. D., Sleeman, A. M., Laskey, R. A. & Blow, J. J. J. Cell Biol. 106, 1–12 (1988).

    Article  CAS  Google Scholar 

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Madine, M., Khoo, CY., Mills, A. et al. MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells. Nature 375, 421–424 (1995). https://doi.org/10.1038/375421a0

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