Possible contribution of oxidative DNA damage 8,5'-purine cyclodeoxynucleosides to progressive neurodegeneration of xeroderma pigmentosum

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790895
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Nara Medical University
• Principal Investigator: IWAMOTO Takaaki 奈良県立医科大学, 医学部, 研究助教 (20448773)
• Research Collaborator: BROOKS P.J. ; NAKANE Hironobu ; HAYASHI Masaharu
• Project Period (FY): 2012-04-01 – 2015-03-31
• 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

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.

Free Research Field

神経病態免疫学