The S.pombe rad12+ gene has recently been isolated and shown to be a homologue of the human BLM gene. Mutations in BLM cause Bloom Syndrome, a disease characterized by high levels of genomic instability and predisposition to cancer. Studies with the rad12 gene product suggest that it negatively regulates the product of the G2 checkpoint rad9 and the loss of rad12 leads to increased rad9p activity. A model is proposed that rad12p is required for proper release from S phase checkpoint arrest. In addition, the human homologue of the S.pombe rad9 gene, HRAD9, has recently also been cloned. Parallel studies in the yeast system and the orthologous human cells will hopefully elucidate the relevant steps in this DNA damage response pathway and help understand the mechanisms underlying Bloom Syndrome and the role of genetic instability in cancer predisposition.
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