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.
| Maftahi, Mohamed; Hope, Justin C; Delgado-Cruzata, Lissette et al. (2002) The severe slow growth of Deltasrs2 Deltarqh1 in Schizosaccharomyces pombe is suppressed by loss of recombination and checkpoint genes. Nucleic Acids Res 30:4781-92 |
| Marchetti, Maria A; Kumar, Sanjay; Hartsuiker, Edgar et al. (2002) A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway. Proc Natl Acad Sci U S A 99:7472-7 |
| Maftahi, M; Han, C S; Langston, L D et al. (1999) The top3(+) gene is essential in Schizosaccharomyces pombe and the lethality associated with its loss is caused by Rad12 helicase activity. Nucleic Acids Res 27:4715-24 |
| St Onge, R P; Udell, C M; Casselman, R et al. (1999) The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1. Mol Biol Cell 10:1985-95 |
| Kaur, B; Fraser, J L; Freyer, G A et al. (1999) A Uve1p-mediated mismatch repair pathway in Schizosaccharomyces pombe. Mol Cell Biol 19:4703-10 |
