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Dynactin is involved in a checkpoint to monitor cell wall synthesis in Saccharomyces cerevisiae

Abstract

Checkpoint controls ensure the completion of cell cycle events with high fidelity in the correct order. Here we show the existence of a novel checkpoint that ensures coupling of cell wall synthesis and mitosis. In response to a defect in cell wall synthesis, S. cerevisiae cells arrest the cell-cycle before spindle pole body separation. This arrest results from the regulation of the M-phase cyclin Clb2p at the transcriptional level through the transcription factor Fkh2p. Components of the dynactin complex are required to achieve the G2 arrest whilst keeping cells highly viable. Thus, the dynactin complex has a function in a checkpoint that monitors cell wall synthesis.

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Figure 1: Perturbation in glucan synthesis induces G2 arrest.
Figure 2: G2 arrest on glucan synthesis perturbation is the result of impairment of Clb2p.
Figure 3: Wac1p is required for G2 arrest induced by the cell wall integrity checkpoint.
Figure 4: Wac1p down-regulates Fkh2p in response to the cell wall integrity checkpoint.
Figure 5: Arp1p functions in the cell wall integrity checkpoint.
Figure 6: Effect of a glucan synthase inhibitor and mnn10Δ on the cell wall integrity checkpoint.
Figure 7: Cell wall integrity checkpoint differs from other checkpoints.
Figure 8: Model of the cell wall integrity checkpoint.

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Acknowledgements

We thank K. Morishita and S. Oshima for the initial work in this study; A. Hirata for electron microscopic analysis; M. Nishizawa, M. Fujino and D. Hirata for plasmids; T. Watanabe for Echinocandin B; K. Homma for critical reading of the manuscript; and M. Imanari and K. Shimane for preparation of the manuscript. Thanks also go to the members of the Laboratory of Signal Transduction for helpful discussions. This work was supported by a grant for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, and by the Institute for Bioinformatics and Research and Development, of the Japan Science and Technology Corporation.

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Correspondence to Yoshikazu Ohya.

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Suzuki, M., Igarashi, R., Sekiya, M. et al. Dynactin is involved in a checkpoint to monitor cell wall synthesis in Saccharomyces cerevisiae. Nat Cell Biol 6, 861–871 (2004). https://doi.org/10.1038/ncb1162

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