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Molecular and Cellular Biology, November 2000, p. 7922-7932, Vol. 20, No. 21
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Schizosaccharomyces pombe Hsk1p Is a Potential Cds1p Target Required for Genome Integrity

Hilary A. Snaith,1,dagger Grant W. Brown,2 and Susan L. Forsburg1,*

Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037-1099,1 and Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada M5S 1A82

Received 15 May 2000/Returned for modification 11 July 2000/Accepted 15 August 2000

The fission yeast Hsk1p kinase is an essential activator of DNA replication. Here we report the isolation and characterization of a novel mutant allele of the gene. Consistent with its role in the initiation of DNA synthesis, hsk1ts genetically interacts with several S-phase mutants. At the restrictive temperature, hsk1ts cells suffer abnormal S phase and loss of nuclear integrity and are sensitive to both DNA-damaging agents and replication arrest. Interestingly, hsk1ts mutants released to the restrictive temperature after early S-phase arrest in hydroxyurea (HU) are able to complete bulk DNA synthesis but they nevertheless undergo an abnormal mitosis. These findings indicate a second role for hsk1 subsequent to HU arrest. Consistent with a later S-phase role, hsk1ts is synthetically lethal with Delta rqh1 (RecQ helicase) or rad21ts (cohesin) mutants and suppressed by Delta cds1 (RAD53 kinase) mutants. We demonstrate that Hsk1p undergoes Cds1p-dependent phosphorylation in response to HU and that it is a direct substrate of purified Cds1p kinase in vitro. These results indicate that the Hsk1p kinase is a potential target of Cds1p regulation and that its activity is required after replication initiation for normal mitosis.

* Corresponding author. Mailing address: Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, CA 92037-1099. Phone: (858) 453-4100, ext. 1341. Fax: (858) 457-4765. E-mail: forsburg{at}salk.edu.

dagger Present address: Institute for Cell and Molecular Biology, Edinburgh EH9 3JR, United Kingdom.

Molecular and Cellular Biology, November 2000, p. 7922-7932, Vol. 20, No. 21
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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