Studies on the molecular mechanisms to regulate the resumption of stalled replication by translesion synthesis at DNA damage sites
| Project/Area Number |
17K00551
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Kobe University |
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Principal Investigator |
YOKOI MASAYUKI 神戸大学, バイオシグナル総合研究センター, 准教授 (00322701)
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| Co-Investigator(Kenkyū-buntansha) |
花岡 文雄 学習院大学, 理学部, 研究員 (50012670)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 損傷乗り越え合成 / 染色体複製 / DNA損傷 / クロマチン / 脱ユビキチン / 染色体複製阻害 / クロマチンリモデリング / 翻訳後修飾 / クロマチン構造変換 |
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| Outline of Final Research Achievements |
The aim of this research is to elucidate the fundamental mechanism(s) which is important for the resumption of stalled DNA replication by translesion synthesis (TLS) at DNA damage sites. DNA replication arrest at DNA lesion induces post-translational modifications (PTM) of TLS factor(s) such as replication accessary protein PCNA and/or TLS polymerase(s) on chromatin. In order to clarify how TLS governs and controls the resumption of chromosomal replication stalled at the DNA damage on chromatin, the effects of PTM on the function of TLS factors and its relation on chromatin organization were studied. As a result of analysis, new discoveries regarding the stability control of TLS polymerase, the relation of TLS and chromatin organization, and small molecules which inhibit TLS polymerase were obtained.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題で得られた成果は、紫外線や化学物質などの環境由来の原因で生じたDNA損傷が原因で停滞した染色体複製の再開を担うTLS機構の統括・制御機構を明らかにする上で重要な知見である。この他、生細胞イメージングの数値解析で用いたソフトを独自にプログラミングするなど技術的なオリジナリティも高く、さらに、POLHを標的とした創薬につながる新たな発見もあったことなどから、当該研究分野の発展に対する貢献が大いに期待できる点で学術的に意義がある。また、環境リスク評価やがん治療などへの幅広い展開も期待でき、これらは社会的ニーズと関心が高い点で社会的意義があると言える。
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Report
(4 results)
Research Products
(20 results)
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[Presentation] Effect of Polκ deficiency on benzo[a]pyrene-induced tumorigenesis2018
Author(s)
Akagi, J., Cho, Y-M., Toyoda, T., Yokoi, M., Hanaoka, F., Ohmori, H., Ogawa, K.
Organizer
The 5th DNA polymerase meeting
Related Report
Int'l Joint Research
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[Presentation] Benzo[a]pyrene-induced tumorigenesis in Polκ-knockout mice2018
Author(s)
Akagi, J., Cho, Y-M., Toyoda, T., Yokoi, M., Hanaoka, F., Ohmori, H., Ogawa, K.
Organizer
The 11th 3R+3C Symposium
Related Report
Int'l Joint Research
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[Presentation] N7-glycidamide-dG adduct inhibits DNA replication in mammalian cells2018
Author(s)
Akagi, J., Yokoi, M., Cho, Y-M., Yamamoto, J., Mizuta, Y., Iwai, S., Hanaoka, F., Ogawa, K.
Organizer
第41回日本分子生物学会年会
Related Report
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[Presentation] Analysis of contribution of Polκ to benzo[a]pyrene-induced tumorigenesis2018
Author(s)
Akagi, J., Cho, Y-M., Toyoda, T., Mizuta, Y., Yokoi, M., Hanaoka, F., Ohmori, H., Ogawa, K.
Organizer
日本薬学会第138年会
Related Report
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[Presentation] Contribution of Polκ to tumorigenesis in the forestomach of benzo[a]pyrene-fed mice2017
Author(s)
Akagi, J., Cho, Y-M., Toyoda, T., Mizuta, Y., Yokoi, M., Hanaoka, F., Ohmori, H., Ogawa, K.
Organizer
ComBio2017
Related Report
