Molecular mechanisms of mutation induction and suppression by DNA polymerase zeta
Project/Area Number |
17K12824
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Risk sciences of radiation and chemicals
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Research Institution | Hiroshima University |
Principal Investigator |
Suzuki Tetuya 広島大学, 医系科学研究科(薬), 助教 (20573950)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | 損傷乗り越えDNA合成 / DNAポリメラーゼζ / 変異 / DNA損傷 / 損傷乗り越え合成 / DNA修復 / 環境変異原 / 癌 |
Outline of Final Research Achievements |
DNA polymeraseζ(polζ), which is one of translesion DNA polymerases, extends several nucleotides in an error-prone manner bypass through DNA lesions. In this study, the mechanisms of mutagenesis by polζin replication across benzopyrene diol epoxide-guanine adduct (BPDE-dG) were analyzed. BPDE-dG in the lagging strand template induced more mutations in cells expressing low-fidelity polζ than that in the leading strand template. Moreover, mismatch repair could not suppress mutations mediated by translesion DNA synthesis across BPDE-dG by polζ.
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Academic Significance and Societal Importance of the Research Achievements |
DNA polymeraseζが損傷乗り越えDNA合成時に誘発する変異に合成鎖が影響しうることを明らかにすることができた。また、ミスマッチ修復はそれらの変異を抑制しない可能性も示した。今後、さらにその他の因子との関連を研究することによりPolζによる変異誘発の分子機構の解明と発癌との関連を明らかにできることが期待される。また、本研究により開発したノックインによる標的遺伝子への変異導入法は効率的なモデル細胞/動物の作製への応用も期待される。
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Report
(4 results)
Research Products
(8 results)