| Project/Area Number |
11101003
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Iwate College of Nursing (2001-2003)
National Institute of Genetics (1999-2000) |
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Principal Investigator |
OGAWA Tomoko Iwate College of Nursing, Professor, 看護学科, 教授 (80028208)
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| Co-Investigator(Kenkyū-buntansha) |
SHINOHARA Akira Osaka University, Protein Res.Inst., Professor, 蛋白質研究所, 教授 (00252578)
TSUKAMOTO Yasumasa Iwate College of Nursing, Assistant Professor, 看護学科, 講師 (80341725)
OGAWA Hideyuki Iwate College of Nursing, Professor, 看護学科, 学長 (70028207)
SHINOHARA Miki Osaka University, Protein Res.Inst., Research Associate, 蛋白質研究所, 助手 (80335687)
田中 茂生 国立遺伝学研究所, 細胞遺伝研究系, 助手 (10281586)
太田 力 国立遺伝学研究所, 細胞遺伝研究系, 助手 (10290892)
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| Project Period (FY) |
1999 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥274,900,000 (Direct Cost: ¥238,000,000、Indirect Cost: ¥36,900,000)
Fiscal Year 2003: ¥52,000,000 (Direct Cost: ¥40,000,000、Indirect Cost: ¥12,000,000)
Fiscal Year 2002: ¥52,000,000 (Direct Cost: ¥40,000,000、Indirect Cost: ¥12,000,000)
Fiscal Year 2001: ¥55,900,000 (Direct Cost: ¥43,000,000、Indirect Cost: ¥12,900,000)
Fiscal Year 2000: ¥50,000,000 (Direct Cost: ¥50,000,000)
Fiscal Year 1999: ¥65,000,000 (Direct Cost: ¥65,000,000)
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| Keywords | melotic recombination / Mre11 / Rad5O / Xrs2 complex / DNA homology search by Rad51・Rad52 / Domain structure of Xrs2 / Tell-Mre11 checkpoint pathway / recombination specific helicase MER3 / Roles of rad52 in recombination / No need of Xrs2 in DNA damage repair / 制限酵素SceI / Xrs2のMre11結合領域 / 組換えDNA修復合成 / Sae2のドメイン構造 / Xrs20複合体foci / Rad51蛋白質 / Xrs2の機能ドメイン / テロメア長維持 / DNA二重鎖切断修復 / DNA複製フォークの再生 / テロメアG鎖の二次構造認識 / Mrell-Rad50-Xrs2複合体 / Tell-Mrellチェックポイント経路 / Mre11蛋白質の機能制御 / DNA傷害修復でのMre11の役割 / テロメアG-rich構造を認識するMre11 / Mre11のリン酸化の役割 / Mer3蛋白質 / Mer3の交叉型組換えと染色体分配の役割 / 減数分裂期組換 / DNA二重連鎖切断の修復 / Mre11,Rad50,Xrs2蛋白質 / RAD51の転写制御 / Mre11 DNA結合活性 |
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| Research Abstract |
A recombination function is required for repair of DNA breakages, overcome of DNA replication-arrest at a DNA lesion and maintenance of telomere length. We are interested in how multiple functions are produced by a single recombination protein. We selected a Mre11/rad50/Xrs2 complex (MRX), Rad51 and Rad52 as representatives, and investigated mechanisms that give full play to their multiple functioning ability. The followings are main results obtained during this research term.
We analyzed domains of Xrs2 which control the functions of MRX, and found (1)Xrs2 binds to Mre11 with a 32 amino-acid domain (MBX) near the C-terminus, and transports Mre11 into the nucleus. (2)Xrs2 is no more required for DNA damage repair if Mre11 has been transported into the nucleus. (3)For telomere elongation and meiotic recombination, in addition to the MBX, its C-terminal adjacent 104, and its N-terminal adjacent 49-, amino-acid domain are needed, respectively.
I.We found a new checkpoint pathway, Te11-Mre11, that is specific to DNA double-strand breakage (DSB), In mitotic cells, Rad53 and Rad9 and in meiotic cells, Mre4/Mek1, are required, respectively. The MRX plays a sensor against the DSB, activates the pathway, and proceeds recombination under the guidance of the activated pathway.
II.It is a new finding that not only rad51but also rad52 are necessary for DNA homology search. Rad51-Rad52-single-stranded DNA is the complex to do it. Rad52 is also required at the latest stage of recombination, production of a final recombinant molecule.
III.A new helicase gene MER3 was found which is specific to meiotic recombination. As a frequency of meiotic crossover specifically decreases in this mutant, determination of recombinant type, crossover type or gene conversion type, is probably carried out during a process of formation of recombination intermediate, not at the resolution stage of the recombination intermediate as assumed.
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