| Project/Area Number |
16H02957
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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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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Tokyo Metropolitan University |
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Principal Investigator |
hirota kouji 首都大学東京, 理学研究科, 教授 (00342840)
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| Research Collaborator |
ABE Takuya
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | DNA損傷 / 複製 / 変異 / 損傷乗り越え / DNA複製 / ポリメラーゼ / 修復 |
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| Outline of Final Research Achievements |
Genome replication is stalled by unrepaired damage, potentially leading to fork collapse, mutagenesis, and genome instability. Eukaryotic cells have evolved several mechanisms to complete replication beyond a damaged template. The first is translesion DNA synthesis (TLS), which employs specialized DNA polymerases, including Polymerase η to permit continued replication beyond the damaged template. A second mechanism, in which DNA primases play a role, involves the repriming of DNA synthesis downstream from the lesion or structure. A third mechanism, in which DNA polymerase delta continues replication across damaged template, leading mutagenic replication. In this study, we analyzed relationship between these three classes of DNA damage tolerance systems and found these mechanisms complementary play roles. Moreover, we also analyzed the relationship in Y-family TLS polymerases (Pol-eta, iota and kappa) and found the division of labor in these enzymes by the type of DNA damages.
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| Academic Significance and Societal Importance of the Research Achievements |
この研究ではDNA損傷応答に関わる３つの経路の相補性を明らかにした。このような経路間の相補的関係性は、近年新しいガン治療への応用に期待が向けられている。ガン細胞の一般的性質としてなんらかのゲノム維持システムが変異で減弱していることが知られている。この減弱経路と相補的関係にある経路を阻害することでガン細胞を特異的に細胞死に追い込むことが可能である。本研究で得られた知見を今後さらに発展させ、さらなるポリメラーゼ、ゲノム維持ネットワークを包括的に理解することで革新的なガン治療に繋げていきたいと考えている。
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