2006 Fiscal Year Final Research Report Summary
Molecular pathological analysis of defects in DNA base excision repair system using gene modified mice
| Project/Area Number |
16390119
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Kyushu University |
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Principal Investigator |
TSUCHIMOTO Daisuke Kyushu University, Med.Inst.Bioreg., Research Associate, 生体防御医学研究所, 助手 (70363348)
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| Co-Investigator(Kenkyū-buntansha) |
NAKABEPPU Yusaku Kyushu University, Med.Inst.Bioreg., Professor, 生体防御医学研究所, 教授 (30180350)
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| Project Period (FY) |
2004 – 2006
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| Keywords | oxidative stress / 8-oxoguanine / neurodegeneration / Parkinson's disease / Huntington's disease / mitochondrial genome / nuclear genome / cell death |
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| Research Abstract |
Using gene modified mice, we have revealed the followings,
(A) Accumulations of nucleic acids with oxidized bases in genomic DNA or nucleotide pool in nucleus, cytoplasm or mitochondria cause cell death through at least two different pathways.
(B) Defects in repair enzymes for DNA with damaged bases including basic sites or defects in cleaning enzymes for nucleotides with damaged bases cause mutagenesis, cell cycle arrest or cell death at cell level, which result in dysfunction of brain neuron, dyshematopoiesis, growth retardation, cardiodysfunction, or increase of tumorigenesis in mouse individuals.
Using human peripheral lymphocytes, we have revealed the following,
(C) Typical oxidized purine, 8-oxo-guanine (8-oxoG) is unevenly distributed in the normal human genome and the distribution pattern is conserved among different individuals. Moreover, 8-oxoG might be one of the main causes of frequent recombinations and SNPs in human genome.
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