| Project/Area Number |
20570007
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Genetics/Genome dynamics
|
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| Research Institution | Fukuoka Dental College |
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Principal Investigator |
HIDAKA Masumi Fukuoka Dental College, 歯学部, 教授 (80238310)
|
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| Co-Investigator(Renkei-kenkyūsha) |
NAKATSU Yoshimichi 九州大学, 医学(系)研究院, 准教授 (00207820)
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| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | DNA損傷 / アルキル化剤 / アポトーシス / 遺伝子トラップ法 / 突然変異 / 発がん抑制 / 分子遺伝学 / ミスマッチ修復タンパク質 |
|---|
| Research Abstract |
O^6-Methylguanine (O^6-mG), produced in DNA by the action of simple alkylating agents, induces base mispairing during DNA replication and is thus responsible for the induction of mutations as well as tumors. To prevent such an outcome, organisms possess a mechanism to eliminate cells carrying O^6-mG by inducing apoptosis in a mismatch repair protein-dependent manner. To understand the molecular mechanism of O^6-mG-induced apoptosis, we carried out retrovirus-mediated gene-trap mutagenesis, followed by the selection of MNU-resistant clones from MNU-sensitive Mgmt^<-/-> cells. One of the mutants has an insertional mutation in a novel gene, designated Mapo1, and was unable to induce mitochondrial membrane depolarization and caspase-3 activation, hallmarks for the induction of apoptosis, after treatment with MNU. The flag-tagged MAPO1 protein expressed in cells was revealed to be associated with FLCN and AMPK. By the introduction of siRNAs specific for these genes, the production of sub-G_1 population of cells following MNU treatment was severely suppressed, suggesting the important role of MAPO1-containing protein complex in the induction of apoptosis triggered by O^6-mG.
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