2009 Fiscal Year Final Research Report
Genomic damage and cancer cell death caused by reactive oxygen species
| 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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| 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 |
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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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Research Products
(60 results)
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[Journal Article] A Role for Oxidized DNA Precursors in Huntington's Disease-Like Striatal Neurodegeneration.2008
Author(s)
De Luca G, Russo MT, Degan P, Tiveron C, Zijno A, Meccia E, Ventura I, Mattei E, Nakabeppu Y, Crescenzi M, Pepponi R, Pezzola A, Popoli P, Bignami M
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Journal Title
PLoS Genet 4
Pages: e1000266
Peer Reviewed
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