Fission yeast rad12+ regulates cell cycle checkpoint control and is homologous to the Bloom's syndrome disease gene.
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.
Davey
S
S
Department of Oncology, Queen's University, Kingston, Ontario, Canada. sd13@post.queensu.ca
Han
C S
CS
Ramer
S A
SA
Klassen
J C
JC
Jacobson
A
A
Eisenberger
A
A
Hopkins
K M
KM
Lieberman
H B
HB
Freyer
G A
GA
D000251:Adenosine Triphosphatases / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair; D005656:Fungal Proteins; D053484:RecQ Helicases; D016196:S Phase; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D014466:Ultraviolet Rays / Q000009:adverse effects
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; C069930:rad9 protein; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; C106462:Rqh1 protein, S pombe