| Project/Area Number |
11558067
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | Tohoku University |
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Principal Investigator |
YAMAMOTO Kazuo Tohoku University, Graduate School of Life Sciences, Professor, 大学院・生命科学研究科, 教授 (20093536)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Sakae Okayama University, Faculty of Science, Research Associate, 理学部, 助手 (20226989)
IDE Hiroshi Tohoku University, Graduate School of Life Sciences, Professor, 大学院・生命科学研究科, 教授 (70022704)
YAMAMOTO Hiroaki Tohoku University, Graduate School of Life Sciences, Associate Professor, 大学院・生命科学研究科, 助教授 (40174809)
SUZUKI Itaru Pola Cosmetics, Researcher, 皮膚科学研究部, 研究員
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥8,800,000 (Direct Cost: ¥8,800,000)
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| Keywords | melanocyte / melanin producing cell / DNA repair / UV sensitivity / 5' UTR region of tyrosinase / phosphorilation / triplex / UvrA and UvrR protein / DNA修復能 / メラニン色素産生能 / チロシナーゼ / MSH / pink-eyed / ピリミジン2量体 / 光回復酵素遺伝子 / トランスジェニックマウス / 5'非翻訳領域 / melanocortin-1 receptor / 6-4付加体 / 色素性乾皮症A群 / 色素生産能 / メラニン産生 / αMSH / 固相化 |
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| Research Abstract |
This project has been intended to devise system that can monitor individual UV sensitivity by measuring transcriptional expression of tyrosinase or repair genes, which is known to defend from the deleterious effects of UV radiation.
1) The 5' upstream regulatory region of the mouse tyrosinase gene contains a long (GA)n sequence, that may be capable adopting a triple-helical conformation (triplex). The results suggest that the 3'non-coding RNA fragments of mouse tyrosinase transcripts suppress its own expression at the transcriptional level. This might occur by preventing cell type-specific protein factor(s) from binding to the regulatory cis-elements in the 5' upstream region of the gene, possibly through a triplex formation.2) Tyrosinase is the key enzyme for synthesizing melanin pigments, which primarily determine mammalian skin coloration. We provide evidence that 5'flanking sequences from nonmammalian genes are functional in vivo by producing transgenic mice. 3) Microphthalmia-assoc
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iated transcription factor (MITF) plays a critical role in the development of both neural-crest-derived melanocytes and optic cup-derived retinal pigmented epithelium (RPE). We found that melanocyte development depends critically on a single Mitf isoform, Mitf-M. 4) We have established an in situ hybridization technique to investigate mRNA levels of pro-opiomelanocortin, tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, P-protein, Pmel-17/gp100, and microphthalmia-associated transcription factor. Results suggest that the mechanism of the tanning response of human skin may involve the transcriptional regulation of certain pigmentary genes. 5) Using an antibody to detect UV damage and anti-UvrA antibody, we measured the repair ability of recA strain of E. coli. Our results indicate that constitutive level of UvrA protein in the recA cells results in constitutive levels of active UvrABC nuclease which is not enough to operate full nucleotide excision repair (NER), thus leading to extreme UV sensitivity. Less
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