Elucidation of the molecular mechanism of the apoptosis pathway triggered by alkylated base lesions
| Project/Area Number |
23701065
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Fukuoka Dental College |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | アポトーシス / アルキル化剤 / ミスマッチ修復 / 遺伝子トラップ法 |
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| Research Abstract |
O6-Methylguanine is especially mutagenic. Cells containing this lesion are eliminated by the mismatch repair (MMR)-dependent apoptosis. After attempts to identify new genes related to the induction of MMR dependent apoptosis, a novel gene named as MAPO2 was identified. To elucidate the function of the MAPO2 gene product in the apoptosis pathway, a MAPO2 knocked-down human cell line was constructed. After exposure to an alkylating agent, MNU, control HeLa MR cells and the knockdown cells underwent cell cycle arrest at G2/M phase, however, the production of the sub-G1 population in the knockdown cells was significantly suppressed in comparison to that in HeLa MR cells. Moreover, the activation of BAK and caspase-3, and depolarization of mitochondrial membrane, hallmarks for the induction of apoptosis, were also suppressed in the knockdown cells. These results suggest that the MAPO2 gene product might positively contribute to the induction of apoptosis triggered by O6-methylguanine.
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Report
(4 results)
Research Products
(6 results)
