Molecular mechanism of Neuronal cell death and transcriptional suppression associated with oxidative DNA stress.
| Project/Area Number |
16590817
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Niigata University |
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Principal Investigator |
IGARASHI Shuichi Niigata University, Medical and Dental Hospital, Lecture, 医歯学総合病院, 講師 (60345519)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | aprataxin / APTX / SSBR / ataxia / EAOH / DAN repair / degeneration / phosphatase / exonuclease |
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| Research Abstract |
Aprataxin (APTX) is a causative gene product for early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH/AOA1), an autosomal recessive disorder of spinocerebellar degeneration with peripheral axonal neuropathy. APTX is a member of histidine triad (HIT) family proteins, which probably have hydrolase activity. A folk head associated (FHA) domain of the APTX binds to X-ray repair cross-complementing group 1 protein (XRCC1), which is a scaffold protein for DNA single strand break repair (SSBR). Furthermore, the lymphoblastoid cells of EAOH/AOA1 patients are vulnerable to H_2O_2 or alkylating-agents which induced DNA single strand break. These findings suggest that APTX acts in SSBR machinery. We showed that APTX had a bidirectional DNA exonuclease activity preferring single-stranded DNA to double-stranded DNA by in vitro synthetic oligonucleotide assay. APTX also restored blocked 3'-termini, 3'-phosphate or 3'- phosphoglycolate (PG), to 3'-OH termini. We assume that deficit of APTX activity, which restores blocked 3'-termini in SSBR, leads to accumulate DNA single strand breaks in neurons then causes neuronal cell death
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Report
(3 results)
Research Products
(15 results)
