DNA damage repair in SCA1 pathology
| Project/Area Number |
24700374
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TAMURA Takuya 東京医科歯科大学, 難治疾患研究所, 助教 (80396647)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ショウジョウバエ / DNA損傷修復 / 神経変性疾患 / ポリグルタミン病 / 脊髄小脳失調症1型 / システム生物学 / 寿命 / 国際研究者交流イギリス |
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| Research Abstract |
We tested the effect of their overexpression on lifespan and developmental viability in SCA1 Drosophila model expressing ATX1-82Q. We identified genes previously unknown to be involved in CAG-/polyQ-related pathogenesis that function in multiple DNA damage repair systems. Beyond the significance of each repair system, systems biology analyses unraveled the core networks connecting positive genes in the gene screen that could contribute to SCA1 pathology. In particular, RpA1, which had the largest effect on lifespan in the SCA1 fly model, was located at the hub position linked to such core repair systems, including homologous recombination (HR). We revealed that ATXN1 actually interacted with RpA1. Furthermore, mutant but not normal ATXN1 impaired the dynamics of RpA1 in the nucleus after DNA damage. In addition, chemical and genetic inhibitions of Chk1 elongated lifespa. Collectively, we elucidated core networks for DNA damage repair in SCA1 that might include the aberrant usage of HR.
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Report
(3 results)
Research Products
(40 results)
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[Journal Article] Systems biology analysis of Drosophila in vivo screen data elucidates core networks for DNA damage repair in SCA1.2014
Author(s)
Barclay, S.S., Tamura, T., Ito H., Fujita, K., Tagawa, K., Shimamura, T., Katsuta, A., Shiwaku, H., Sone, M., Imoto, S., Miyano, S. and Okazawa, H.
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Journal Title
Hum Mol Genet
Volume: 23
Issue: 5
Pages: 1345-1364
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A functional deficiency of TERA/VCP/p97 contributes to impaired DNA repair in multiple polyglutamine diseases.2013
Author(s)
Fujita K, Nakamura Y, Oka T, Ito H, Tamura T, Tagawa K, Sasabe T, Katsuta A, Motoki K, Shiwaku H, Sone M, Yoshida C, Katsuno M, Eishi Y, Murata M, Taylor JP, Wanker EE, Kono K, Tashiro S, Sobue G, La Spada AR, Okazawa H.
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Journal Title
Nat Commun.
Volume: 4
Issue: 1
Pages: 1816-1816
DOI
Related Report
Peer Reviewed
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[Journal Article] Sox2 transcriptionally regulates Pqbp1, an Intellectual Disability-Microcephaly causative gene, in neural stem progenitor cells.2013
Author(s)
Li, C., Ito, H., Fujita, K., Shiwaku, H., Yunlong Qi, Y., Tagawa, K., Tamura, T., Okazawa, H.
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Journal Title
PLOS ONE
Volume: 8
Issue: 7
Pages: e68627-e68627
DOI
Related Report
Peer Reviewed
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[Presentation] Replication-dependent DNA repair in SCA1 pathology2013
Author(s)
Tamura, T., Barclay, S, S., Fujita, K., Ito, H., Motoki, K., Shimamura, T., Tagawa, K., Katsuta, A., Shiwaku, H.,Sone, M., Tagawa, K., Imoto, S., Miyano, S., Okazawa, H.
Organizer
Neuro2013
Place of Presentation
Kyoto International Conference Center, Kyoto, Tokyo
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