| Project/Area Number |
18K19152
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 37:Biomolecular chemistry and related fields
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| Research Institution | Konan University |
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Principal Investigator |
Naoki Sugimoto 甲南大学, 先端生命工学研究所, 教授 (60206430)
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| Co-Investigator(Kenkyū-buntansha) |
建石 寿枝 甲南大学, 先端生命工学研究所, 講師 (20593495)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | がん細胞 / カリウムイオン / 非二重らせん構造 / 転写変異 / がん遺伝子 / 定量的解析 / 神経変性疾患 / 転写調節 / 細胞内環境 / 遺伝子発現変異 / 熱力学的解析 |
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| Outline of Final Research Achievements |
In this study, we investigated physicochemically how changes of intracellular chemical environments influence G-quadruplex formation and transcription during tumor progression in vitro and in cells. In vitro, the stable G-quadruplex formation inhibits transcription in a solution containing 150 mM KCl (standard condition in cells). As K+ concentration decreases, which decreases G-quadruplex stability, transcript production from templates with G-quadruplex-forming potential sequences in c-myc gene increases. In normal cell, the trend in transcript productions was similar to that in experiments in vitro, that is, transcription efficiency inversely correlated with G-quadruplex stability. Interestingly, higher transcript levels were produced from templates with G-quadruplex-forming potential in the highly metastatic breast cancer cell than in the normal cell. Our results suggest that in normal cell, K+ ions attenuate the transcription of certain oncogenes by stabilizing G-quadruplexes.
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| Academic Significance and Societal Importance of the Research Achievements |
DNAは塩基の並びによって遺伝情報を保持している。一方でDNAは標準的な二重らせん構造だけでなく、非二重らせん構造も形成するが、非二重らせん構造の細胞内における役割は未だ明らかでなかった。本研究では、塩基の並びが同じDNAでも、正常細胞では四重らせんを優先的に形成して、がんの進行を促す遺伝子発現を抑制する一方、悪性がん細胞では四重らせん構造が解離し、がん遺伝子の転写を活性化することを見出した。
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