Possible contribution of oxidative DNA damage 8,5'-purine cyclodeoxynucleosides to progressive neurodegeneration of xeroderma pigmentosum
| Project/Area Number |
24790895
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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 |
Neurology
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| Research Institution | Nara Medical University |
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Principal Investigator |
IWAMOTO Takaaki 奈良県立医科大学, 医学部, 研究助教 (20448773)
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| Research Collaborator |
BROOKS P.J.
NAKANE Hironobu
HAYASHI Masaharu
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 酸化的DNA損傷サイクロプリン / 色素性乾皮症 / ヌクレオチド除去修復 / 神経障害 / 国際情報交換, アメリカ |
|---|
| Outline of Final Research Achievements |
Xeroderma pigmentosum A group (XP-A) patients develop progressive neurological disease, which has been hypothesized to be associated with the accumulation of a type of oxidative DNA damage called purine 8,5’-cyclo- 2’-deoxynucleosides. Thus, we generated a monoclonal antibody (CdA-1) specific for 8,5’-cyclo-2’-deoxyadenosine (cyclo-dA). An immunoassay using CdA-1 revealed a linear dose response between known amounts of cyclo-dA in oligonucleotides and the antibody binding to them. The quantitative immunoassay revealed that treatment with Fenton-type reagents dose-dependently produces cyclo-dA in DNA. Moreover, immunofluorescent analysis enabled the visualization of cyclo-dA in human cells, which had been transfected with oligonucleotides containing cyclo-dA. Thus, the CdA-1 antibody is a valuable tool for the detection and quantification of cyclo-dA in DNA, and may be useful for characterizing the mechanism(s) underlying the development of XP neurological disease.
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Report
(4 results)
Research Products
(8 results)
