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Mol Cell Biol, May 1998, p. 2721-2728, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Fission Yeast rad12+ Regulates Cell Cycle Checkpoint Control and Is Homologous to the Bloom's Syndrome Disease Gene

Scott Davey,1,2,* Christine S. Han,3 Sarah A. Ramer,1 Jennifer C. Klassen,1 Adam Jacobson,3 Andrew Eisenberger,3 Kevin M. Hopkins,4 Howard B. Lieberman,4 and Greg A. Freyer3

Cancer Research Laboratories1 and Departments of Oncology and Pathology,2 Queen's University, Kingston, Ontario K7L 3N6, Canada, and Department of Environmental Health Sciences, School of Public Health,3 and Center for Radiological Research,4 Columbia University, New York, New York 10032

Received 22 September 1997/Returned for modification 2 December 1997/Accepted 10 February 1998

The human BLM gene is a member of the Escherichia coli recQ helicase family, which includes the Saccharomyces cerevisiae SGS1 and human WRN genes. Defects in BLM are responsible for the human disease Bloom's syndrome, which is characterized in part by genomic instability and a high incidence of cancer. Here we describe the cloning of rad12+, which is the fission yeast homolog of BLM and is identical to the recently reported rhq1+ gene. We showed that rad12 null cells are sensitive to DNA damage induced by UV light and gamma  radiation, as well as to the DNA synthesis inhibitor hydroxyurea. Overexpression of the wild-type rad12+ gene also leads to sensitivity to these agents and to defects associated with the loss of the S-phase and G2-phase checkpoint control. We showed genetically and biochemically that rad12+ acts upstream from rad9+, one of the fission yeast G2 checkpoint control genes, in regulating exit from the S-phase checkpoint. The physical chromosome segregation defects seen in rad12 null cells combined with the checkpoint regulation defect seen in the rad12+ overproducer implicate rad12+ as a key coupler of chromosomal integrity with cell cycle progression.

* Corresponding author. Mailing address: Cancer Research Laboratories, Botterell Hall, Room A309A, Queen's University, Kingston, Ontario K7L 3N6, Canada. Phone: (613) 545-6926. Fax: (613) 545-6830. E-mail: sd13{at}post.queensu.ca.

Mol Cell Biol, May 1998, p. 2721-2728, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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