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The Cdt1 protein is required to license DNA for replication in fission yeast

Author

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  • Hideo Nishitani

    (Imperial Cancer Research Fund
    Graduate School of Medical Science, Kyushu University)

  • Zoi Lygerou

    (Imperial Cancer Research Fund
    University of Patras)

  • Takeharu Nishimoto

    (Graduate School of Medical Science, Kyushu University)

  • Paul Nurse

    (Imperial Cancer Research Fund)

Abstract

To maintain genome stability in eukaryotic cells, DNA is licensed for replication only after the cell has completed mitosis, ensuring that DNA synthesis (S phase) occurs once every cell cycle1. This licensing control is thought to require the protein Cdc6 (Cdc18 in fission yeast) as a mediator for association of minichromosome maintenance (MCM) proteins with chromatin2,3,4,5,6,7,8,9,10. The control is overridden in fission yeast by overexpressing Cdc18 (ref. 11) which leads to continued DNA synthesis in the absence of mitosis12. Other factors acting in this control have been postulated13 and we have used a re-replication assay to identify Cdt1 (ref. 14) as one such factor. Cdt1 cooperates with Cdc18 to promote DNA replication, interacts with Cdc18, is located in the nucleus, and its concentration peaks as cells finish mitosis and proceed to S phase. Both Cdc18 and Cdt1 are required to load the MCM protein Cdc21 onto chromatin at the end of mitosis and this is necessary to initiate DNA replication. Genes related to Cdt1 have been found in Metazoa and plants (A. Whitaker, I. Roysman and T. Orr-Weaver, personal communication), suggesting that the cooperation of Cdc6/Cdc18 with Cdt1 to load MCM proteins onto chromatin may be a generally conserved feature of DNA licensing in eukaryotes.

Suggested Citation

  • Hideo Nishitani & Zoi Lygerou & Takeharu Nishimoto & Paul Nurse, 2000. "The Cdt1 protein is required to license DNA for replication in fission yeast," Nature, Nature, vol. 404(6778), pages 625-628, April.
    • Handle: RePEc:nat:nature:v:404:y:2000:i:6778:d:10.1038_35007110
    DOI: 10.1038/35007110
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    Cited by:

    1. Aftab Amin & Cheung Man Hei & Chun Liang & Aftab Amin & Cheung Man Hei & Chun Liang & Chun Liang & Aftab Amin & Cheung Man Hei & Chun Liang, 2019. "DNA Replication-Initiation Proteins in Eukaryotic Cells," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 22(5), pages 17042-17049, December.

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