Molecular basis of spatiotemporal regulation of damage tolerance pathways to control the induced mutagenesis
| Project/Area Number |
18H03371
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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 | 一般 |
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| Review Section |
Basic Section 63020:Radiation influence-related
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| Research Institution | Nagoya University |
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Principal Investigator |
Masuda Yuji 名古屋大学, 医学系研究科(環医), 准教授 (30273866)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Keywords | DNA損傷 / DNA複製 / DNA修復 / DNA損傷トレランス / 突然変異 / 損傷トレランス / 変異 |
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| Outline of Final Research Achievements |
Mutagenesis is one of the critical outcomes of exposure by radiation or environmental mutagens. The molecular mechanism of the induced mutagenesis, which is one of the most important issues in this field, remains to be elucidated. A significant fraction of the induced mutation is generated through a cellular process, so-called DNA damage tolerance. In humans, two sub-pathways are regulated by ubiquitination of PCNA, one of the auxiliary factors of DNA replication; one is the error-prone pathway, translesion DNA synthesis, inducing point mutations, and the other is template switch, which is the error-free, in principle, but has a risk of genomic rearrangements. Therefore, the regulation of the choice of two pathways is a crucial step for the maintenance of genetic stability. In this study, we examined the key molecules involved in the PCNA ubiquitination and deubiquitination of ubiquitinated PCNA.
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| Academic Significance and Societal Importance of the Research Achievements |
DNA損傷トレランスは紫外線などによるDNA損傷から生体を防御する分子機構であるが、一方で、変異誘発の原因となることから、厳密な制御下にあると考えられている。特にがん治療においては、抗がん剤への耐性や、変異誘発に関与することから、分子メカニズムの解明が求められている。DNA損傷トレランスには二つの分子機構が知られており、その二つの分子機構の選択は、紫外線やDNA損傷を誘発する抗がん剤に暴露した細胞の生死や遺伝子変異の誘発リスクを適切に制御する上でとても重要である。本研究成果は、紫外線や抗がん剤などによって誘発されるDNA損傷における生体応答を理解する上での知的基盤を与えるものである。
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Report
(5 results)
Research Products
(21 results)
