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Mrc1 channels the DNA replication arrest signal to checkpoint kinase Cds1

Nature Cell Biology volume 3, pages 966–972 (2001)Cite this article

Abstract

Checkpoint responses change as cells proceed through the cell cycle. Here we describe a novel checkpoint gene in fission yeast, mrc1 (mediator of replication checkpoint), that confers activation of the checkpoint kinase Cds1 to DNA synthesis (S) phase. Mrc1 associates with Cds1 and is required for regulation of Cds1 by the checkpoint kinase Rad3. Mrc1 is regulated by the cell cycle, with the appearance of Mrc1 mRNA and protein coinciding with S phase. We propose that coordinated expression of Mrc1 with replication control proteins helps to ensure activation of the appropriate checkpoint response during DNA replication.

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Figure 1: HU sensitivity of mrc1− cells rescued by cds1+ plasmid.
Figure 2: Mrc1 is required for Cds1 regulation.
Figure 3: Defective S–M checkpoint in mrc1− chk1− cells.
Figure 4: Intact G2–M DNA damage checkpoint in mrc1− cells.
Figure 5: Regulation of Mrc1 protein and mRNA during the cell cycle.
Figure 6: Overproduced Cds1 is activated in HU-treated mrc1− cells.
Figure 7: Two-hybrid interactions between Mrc1 and Cds1.

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Acknowledgements

We thank members of the Scripps Cell Cycle Groups for general support and encouragement. T. Wang kindly provided Cds1 antisera and S. Elledge discussed unpublished results. K.T. received salary support from The Naito Foundation. This research was funded by NIH. Correspondence and requests for materials should be addressed to P.R. Mrc1 is listed as SPAC694.06C in the S. pombe genome database and has the GenBank accession number CAB71844 .

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  1. Departments of Molecular and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Katsunori Tanaka & Paul Russell

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Correspondence to Paul Russell.

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Tanaka, K., Russell, P. Mrc1 channels the DNA replication arrest signal to checkpoint kinase Cds1. Nat Cell Biol 3, 966–972 (2001). https://doi.org/10.1038/ncb1101-966

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