| Project/Area Number |
03454530
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Laboratory animal science
|
|---|
| Research Institution | Kinki University (1993)
Osaka University (1991-1992) |
|---|
Principal Investigator |
MATSUSHIRO Aizo Kinki University, Prof., 生物理工学部, 教授 (00029753)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SHIMADA Kazunori Osaka University, Res.Inst.for Micro. Dis., Prof., 微生物病研究所, 教授 (40037354)
MORITA Takashi Osaka University, Res.Inst.for Micro. Dis., Associate Prof., 微生物病研究所, 助教授 (70150349)
|
|---|
| Project Period (FY) |
1991 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥3,500,000 (Direct Cost: ¥3,500,000)
|
|---|
| Keywords | Homologous recombination / RecA / Higher eukaryotes / DNA repair / Experimantal Model animals / 実験動物 / Rad51 / マウス / 細胞周期 / 高頻度相同組え系 / 酸母 / RAD51 / RAD52 |
|---|
| Research Abstract |
In mammalian cells, gene targeting by homologous recombination is an effective way of generating mutant genes in embryonic stem cells (ES cells) in order to analyze the function of cloned genes. However, the mechanisms of mitotic and meiotic recombination in mammalian cells are still unclear. In budding yeast, Saccharomyces cerevisiae, The RAD51 gene is essential along with other genes of the RAD52 epistasis group for mitotic and meiotic recombination and DNA repair. The Rad51 protein is structurally similar to Escherichia coli RecA protein, which is required in homologous recombination and SOS responses in bacteria. We have isolated a mouse homolog of the yeast RAD51 gene. The amino acid sequence predicted from the gene shows 83% and 55% homology with those of the yeast RAD51 and the E.coli recA product, respectively. The mouse gene complemented a rad51 mutation of S.cerevisiae with sensitivity to methylmethanesulphonate (MMS), which produces double-strand breaks of DNA.This gene is expressed in the thymus, testis, ovary, spleen and intestine, suggesting that its product is involved in mitotic and meiotic recombination in addition to DNA repair. Our isolation of the mouse homolog of the yeast RAD51 supports the view that the mechanism of homologous recombination is essentially the same from prokaryote to higher eukaryote. Molecular investigations of homologous recombination in mammalian cells will provide insights not only into mechanisms for general recombination, but also techniques for more precise and effective manipulation of the mammalian genome for gene targeting and gene therapy.
|
