| Project/Area Number |
20013034
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyushu University |
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Principal Investigator |
NAKABEPPU Yusaku Kyushu University, 生体防御医学研究所, 教授 (30180350)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥18,000,000 (Direct Cost: ¥18,000,000)
Fiscal Year 2009: ¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 2008: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | 酸化ストレス / 8-オキソグアニン / プログラム細胞死 / p53 / MUTYH / 8-oxoguanine / MLH1 / MSH2 / 核DNA / ミトコンドリアDNA / (2)-ヒドロキシアデン / 細胞死 / P53 |
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| Research Abstract |
8-Oxoguanine (8-oxoG) is one of the major oxidative base lesions in DNA or nucleotides, and is highly mutagenic because it can pair with adenine as well as cytosine. To minimize accumulation of 8-oxoG in mammalian genomes, MTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, and OGG1 excises 8-oxoG paired with cytosine in DNA, while MUTYH excises adenine inserted opposite 8-oxoG in template DNA during DNA replication and whose deficiency is known to cause MUTYH-associated familial adenomatous polyposis. We found that the buildup of 8-oxoG in nuclear or mitochondrial DNA initiates MUTYH-dependent cell death, and unveiled its regulatory mechanisms, thus demonstrating that the cell death is crucial for tumor suppression.
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