A rapid, comprehensive system for assaying DNA repair activity and cytotoxic effects of DNA-damaging reagents
Project/Area Number |
24659533
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Dermatology
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Research Institution | Nagasaki University |
Principal Investigator |
OGI Tomoo 長崎大学, 原爆後障害医療研究所, 准教授 (80508317)
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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 |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | ヌクレオチド除去修復 / DNA修復 |
Outline of Final Research Achievements |
Nucleotide excision repair (NER) is most versatile DNA repair process: it prevents cells from genomic instability as it removes various DNA damages arose in the genome. DNA repair assays that can directly measure NER activities are useful for clinical diagnoses and clinical researches including anticancer drug discovery. Unscheduled DNA synthesis (UDS) and recovery of RNA synthesis (RRS) are two commonly used DNA repair endpoints for assessing the activity of NER. We developed a comprehensive procedure for measuring UDS, RRS and cell-sensitivity by the incorporation of ethynyl-nucleoside analogs (EdU and EU) followed by the click-chemistry reaction. The developed system is suitable for a virus-based UDS / RRS / cell-sensitivity complementation tests, by which we can systematically determine the pathogenic gene of a patient with defect in the DNA repair pathways. A typical clinical diagnosis, using human primary fibroblast cells, takes less than 1 week.
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Hypomorphic PCNA mutation underlies a human DNA repair disorder.2014
Author(s)
Baple EL, Chambers H, Cross HE, Fawcett H, Nakazawa Y, Chioza BA, Harlalka GV, Mansour S, Sreekantan-Nair A, Patton MA, Muggenthaler M, Rich P, Wagner K, Coblentz R, Stein CK, Last JI, Taylor AM, Jackson AP, Ogi T, Lehmann AR, Green CM, Crosby AH.
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Journal Title
Journal of Clinical Investigation
Volume: 124
Issue: 7
Pages: 3137-3146
DOI
Related Report
Peer Reviewed
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[Journal Article] PRKDC mutations in a SCID patient with profound neurological abnormalities.2013
Author(s)
Woodbine L, Neal JA, Sasi NK, Shimada M, Deem K, Coleman H, Dobyns WB, Ogi T, §Meek K, §Davies EG, §Jeggo PA.
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Journal Title
The Journal of Clinical Investigation
Volume: 123
Issue: 7
Pages: 2969-2980
DOI
Related Report
Peer Reviewed
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[Journal Article] Malfunction of Nuclease ERCC1-XPF Results in Diverse Clinical Manifestations and Causes Cockayne Syndrome, Xeroderma Pigmentosum, and Fanconi Anemia.2013
Author(s)
Kashiyama, K, Nakazawa, Y, Pilz, DT, Guo, C, Sasaki, K, et al.
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Journal Title
The American Journal of Human Genetics
Volume: 92
Issue: 5
Pages: 807-819
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel syndrome2012
Author(s)
*Ogi T , Walker S, Stiff T, Hobson E, Limsirichaikul S, Carpenter G, Prescott K, Suri M, Byrd P, Matsuse M, Mitsutake N, Nakazawa Y, Vasudevan P, Barrow M, Stewart G, Taylor M, O'Driscoll M, and Jeggo P
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Journal Title
PLoS Genetics
Volume: 8
Issue: 11
Pages: e1002945-e1002945
DOI
NAID
Related Report
Peer Reviewed
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[Presentation] Molecular characterization and functional analysis of XRCC4, a novel pathological gene for radiation sensitivity and developmental abnormalities2014
Author(s)
Guo C, Nakazawa Y, Shimada M, Woodbine L, Jia N, Karata K, Miyazaki H, Lehmann A, Jeggo PA, Ogi T.
Organizer
The 9th 3R Symposium
Place of Presentation
御殿場高原ホテル(静岡県御殿場市)
Year and Date
2014-11-17 – 2014-11-21
Related Report
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[Presentation] ERCC1/XPF deficiency causes three NER- deficient disorders: a patient with various symptoms of xeroderma pigmentosum, Cockayne syndrome & Fanconi anemia.2014
Author(s)
Nakazawa Y, Kashiyama K, Pilz DT, Guo C, Shimada M, Sasaki K, Fawcett H, Wing JF, Lewin SO, Carr L, Li TS, Yoshiura K, Utani A, Hirano A, Greenblatt D, Nardo T, Stefanini M, McGibbon D, Sarkany R, Fassihi H, Mitsutake N, Lehmann AR, Ogi T.
Organizer
The 9th 3R Symposium
Place of Presentation
御殿場高原ホテル(静岡県御殿場市)
Year and Date
2014-11-17 – 2014-11-21
Related Report
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