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Mol Cell Biol, May 1998, p. 2721-2728, Vol. 18, No. 5
Cancer Research
Laboratories1 and
Departments of
Oncology and Pathology,2 Queen's University,
Kingston, Ontario K7L 3N6, Canada, and
Department of
Environmental Health Sciences,
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
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
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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