Strategy for the prediction and control of radiosensitivity based on the life-cycle and homeostasis of the DNA repair system
| Project/Area Number |
21689033
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Radiation science
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000)
Fiscal Year 2011: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2009: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
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| Keywords | 放射線治療生物学 / 癌 / 放射線治療 / ＤＮＡ二重鎖切断修復 / 発現制御 / 翻訳後修飾 / ライフサイクル / ホメオスタシス / 放射線感受性 / DNA二重鎖切断修復 |
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| Research Abstract |
This study aimed to find a new approach to the prediction and control of radiosensitivity through the analyses of the life cycle-how proteins are generated and degraded - and homeostasis-how proteins are protected and recovered from dysfunctional status, such as denaturation - of proteins involved in DNA double-strand break repair through non-homologous end joining.We obtained the following major outcomes. First, we found regions in DNA ligase IV for chromatin binding and stabilization. Second, we found a protein required for the chromatin binding of XRCC4 and also clarified binding region in XRCC4. Third, we created a series of mutants of XRCC4 and XLF. In XRCC4, we found several mutants, other than potential phosphorylation site mutants, with elevated radiosensitivity, suggesting possible involvement of posttranslational modifications other than phosphorylation or protein-protein interaction. These results might show a new strategy for radiosensitization by targeting the protein-protein or protein-chromatin interactions.
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Report
(4 results)
Research Products
(72 results)
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[Journal Article] DNA-PK inhibition causes a low level of H2AX phosphorylation and homologous recombination repair in Medaka (Oryzias latipes) cells. Biochem.2012
Author(s)
Urushihara, Y., Kobayashi, J., Matsumoto, Y., Komatsu, K, Oda, S., Mitani, H.
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Journal Title
Biophys.Res.Commun.
Volume: 429
Issue: 3-4
Pages: 131-136
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel target of Bisphenol A.2012
Author(s)
Ito, Y., Ito, T., Karasawa, S., Enomoto, T., Nashimoto, A., Hase, Y., Sakamoto, S., Ito, T., Mimori, T., Matsumoto, Y., Yamaguchi, Y., Handa, H.
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Journal Title
PLos ONE
Volume: 7(12)
Issue: 12
Pages: e50481-e50481
DOI
Related Report
Peer Reviewed
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[Journal Article] Analysis ofKu and XRCC4 expressions of hypopharyngeal cancer tissues and results treated with chemoradiotherapy.2012
Author(s)
Hayashi, J., Sakata, K., Someya, M., Matsumoto, Y., Satoh, M., Kataya, K., Hori, M., Takagi, M. and Hareyama, M.
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Journal Title
Oncol. Lett.
Volume: 4
Issue: 1
Pages: 151-155
DOI
Related Report
Peer Reviewed
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[Journal Article] Gene Expression Associated with DNA-Dependent Protein Kinase Activity under Normoxia, Hypoxia, and Reoxygenation2011
Author(s)
Tsuchimoto,T., Sakata,K., Someya,M., Yamamoto,H., Hirayama,R., Matsumoto,Y., Furusawa,Y. and Hareyama,M.
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Journal Title
Journal of Radiation Research
Volume: 52
Issue: 4
Pages: 464-471
DOI
NAID
ISSN
0449-3060, 1349-9157
Related Report
Peer Reviewed
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[Journal Article] The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer2011
Author(s)
Someya,M., Sakata,K., Matsumoto,Y., Kamdar,R.P., Kai,M., Toyota,M. and Hareyama,M.
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Journal Title
Brit.J.Cancer
Volume: 104
Issue: 11
Pages: 1724-1729
DOI
Related Report
Peer Reviewed
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[Book] DNARepair-New Research Directions2012
Author(s)
Matsumoto, Y. Imamichi, S., Fukuchi, M., Liu, S., Wanotayan, R., Kuniyoshi, S., Yoshida, K., Mae, Y., Sharma, M.K
Publisher
Edit. Chen,C.
Related Report
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