| Project/Area Number |
13854026
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (S)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Molecular biology
|
|---|
| Research Institution | Kyoto University (2002-2005)
Tokyo Institute of Technology (2001) |
|---|
Principal Investigator |
ISHIKAWA Fuyuki Kyoto University, Graduate School of Biostudies, Professor, 大学院・生命科学研究科, 教授 (30184493)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KANOH Junko Kyoto University, Graduate School of Biostudies, Instructor, 大学院・生命科学研究科, 助手 (10323809)
NABETANI Akira Kyoto University, Graduate School of Biostudies, Instructor, 大学院・生命科学研究科, 助手 (40334495)
|
|---|
| Project Period (FY) |
2001 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥123,240,000 (Direct Cost: ¥94,800,000、Indirect Cost: ¥28,440,000)
Fiscal Year 2005: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2004: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2003: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2002: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2001: ¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000)
|
|---|
| Keywords | telomere / fission yeast / Xenopus / TRF1, TRF2 / Polo-like kinase / DNA replication / DNA polymerase α / end replication problem / 核 / ヘテロクロマチン / OB-fold / 複製 / カエル卵抽出液 / TRF1 / TRF2 / Polo-like kinase / SV40 / 複製フォーク / ALT / チェックポイントRad / Ku蛋白質 / DNA末端結合反応 / サイレンシング / テロメレース / Rap1 / Xenopus卵抽出液 |
|---|
| Research Abstract |
Telomere structures and functions were studied using fission yeast, Xenopus egg extracts and mammalian cultured cells. These model organisms were chosen because they are highly amenable to genetic, biochemical and cell biological analyses, respectively.
1. Novel telomeric components, spRap1,SpRif1,Ccq1,Poz1,were identified in fission yeast.
2. Telomere DNA-binding protein TRF1 was found to associate with and dissociate from chromatin in a cell-cycle-dependent manner in Xenopus egg extracts.
3. Using the SV40 replication system, the molecular mechanism of the end replication problem was analyzed. It was found that telomeric DNA by itself as well as telomere chromatin is not a good substrate for replication reactions.
4. Using murine cells harboring temperature-sensitive DNA polymerase a, it was found that the telomere comprises one of the most vulnerable genomic regions to replication stresses.
5. It was found that epigenetic as well as genetic mechanisms cooperate to maintain the telomere functions.
These studies revealed new aspects of telomere structures and functions, which will extend our understanding of apparently stochastic chromosomal behaviors in aging and cancer cells. Moreover, it became evident that "meta-biology", studying different model organisms in parallel to promote the research in an cross-species interactive manner is highly efficient and productive.
|
