FISSION YEAST RAD12(-CYCLE CHECKPOINT CONTROL AND IS HOMOLOGOUS TO THE BLOOMS-SYNDROME DISEASE GENE() REGULATES CELL)

The human BLM gene is a member of the Escherichia coli recQ helicase f amily, which includes the Saccharomyces cerevisiae SGS1 and human WRN genes. Defects in BLM are responsible for the human disease Bloom's sy ndrome, which is characterized in part by genomic instability and a hi gh incidence of cancer. Here we describe the cloning of rad12(+), whic h 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 t he DNA synthesis inhibitor hydroxyurea. Overexpression of the wild-typ e rad12(+) gene also leads to sensitivity to these agents and to defec ts associated with the loss of the S-phase and G(2)-phase checkpoint c ontrol. We shelved genetically and biochemically that rad12(+) acts up stream from rad9(+), one of the fission yeast G(2) checkpoint control genes, in regulating exit from the S-phase checkpoint. The physical ch romosome segregation defects seen in rad12 null cells combined with th e checkpoint regulation defect seen in the rad12(+) overproducer impli cate rad12(+) as a key coupler of chromosomal integrity with cell cycl e progression.