| Project/Area Number |
13141203
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
SINAGAWA Hideo Osaka-Uieliversity, Research Institute for Microbial Diseases, Professor, 微生物病研究所, 招へい教授 (40029799)
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| Co-Investigator(Kenkyū-buntansha) |
HISHIDA Takashi Research Institute for Microbial Diseases, Associate Professor, 微生物病研究所, 助教授 (60335388)
MORISHITA Takashi Research Institute for Microbial Diseases, Designated Reseacher, 微生物病研究所, 特任研究員 (50273701)
IWASAKI Hiroshi Yokohama City University, Graduate School of Integrated Science, Associate Professor Research Institute for Microbial Diseases, 大学院国際総合科学研究科, 準教授 (60232659)
ISHINO Yoshizumi Kyushu University, Faculty of Agriculture, Professor, 大学院農学研究院, 教授 (30346837)
MORIKAWA Kosuke Dpt. of Structural Biol. Biomolecular Eng. Res. Inst., Director, 所長 (80012665)
筒井 康博 大阪大学, 国立遺伝学研究所, 助手 (00390625)
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| Project Period (FY) |
2001 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥172,700,000 (Direct Cost: ¥172,700,000)
Fiscal Year 2005: ¥44,800,000 (Direct Cost: ¥44,800,000)
Fiscal Year 2004: ¥44,000,000 (Direct Cost: ¥44,000,000)
Fiscal Year 2003: ¥27,700,000 (Direct Cost: ¥27,700,000)
Fiscal Year 2002: ¥27,800,000 (Direct Cost: ¥27,800,000)
Fiscal Year 2001: ¥28,400,000 (Direct Cost: ¥28,400,000)
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| Keywords | genetics / recombination / replication / cancer / radiation / 相同的DNA組換え / Holliday構造 / RuvABC / 出芽酵母 / DNA組換え / 分裂酵母 / MGS1遺伝子 / RAD6-RAD18 |
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| Research Abstract |
In this project, we aimed at elucidating molecular mechanisms of Holliday junction resolutin by E. coli RuvA, RuvB, and RuvC proteins, and finding genes involved in resolution of recombination intermediates in eukaryotes. Our major achievements are as follows.
1. We elucidated three-dimensional structure of RuvA-RuvB protein complex by X-ray crystallography and electron microscopy, and proposed a model of Holliday junction DNA complexed with RuvAB proteins.
2. We identified 10 novel genes involved, in recombination repair in fission yeast and analyzed their functions.
3. We studied the mechanism of branch migration of Holliday junction by RuvAB complex by single-molecule imaging analysis and showed that branch migration is brought by rotation of DNA duplex at the junction.
4. One of the newly found gene, fbh-1, encodes a protein with DNA helicase and F-box motifs. Fbh-1 protein is involved in processing some form of recombination intermediate.
5. We studied the functions of rad60 and rad62 (nse4) genes and found that they are functionally and physically associate with Smc5/6 (Structural Maintenance of Chromosome) complex, and are involved in processing recombination intermediates. We elucidated role of the Rad60 and Smc5/6 complex in checkpoint regulation.
6. We discovered a new recombination repair pathway by the Rad51-Swi5-Sfrl protein complex in fission yeast.
7. We discovered a structure-specific DNA helicase/nuclease named Hef-1 in thermophilic archaea and elucidated the crystal structure. The importance of this enzyme in DNA repair is highlighted by the recent finding that it is an ortholog of one of the genes mutated in Fanconi Anemia, a hereditary disease having a defect in DNA repair.
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