The study of the DNA damage response elicited by NER-provoked secondary damage in mammalian quiescent cells
| Project/Area Number |
24510068
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MATSUNAGA Tsukasa 金沢大学, 薬学系, 教授 (60192340)
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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 |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ヌクレオチド除去修復 / DNA損傷応答 / ssDNAギャップ / DNA二本鎖切断 / シグナル伝達 / ゲノム安定性 / 休止期 / DSB / ATM / ATR / 静止期 / ヒストンH2AX |
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| Outline of Final Research Achievements |
In this study, we tried to clarify the nucleotide excision repair (NER)-related DNA structure(s) activating the signal transduction pathways and their biological impacts. We found that, under the quiescent condition, DSB (DNA double-strand break) is generated in an NER-dependent manner, in addition to the predicted single-stranded regions. In NER-proficient cells arrested in G0 phase, UV exposure activates ATM signaling pathway, which leads to the accumulation of DSV-related factors. Importantly, A-T cells are more sensitive to UV compared with normal cells when exposed under quiescent but not exponentially growing condition. Finally, we show that the NER-dependent H2AX phosphorylation is also observed in peripheral T lymphocytes and hematopoietic stem cells from mice. These all results suggest that in vivo quiescent cells may suffer from the mixed types of DNA lesions such as ssDNA gaps and DSB after UV or chemical exposure generating NER substrates.
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Concanavalin A-mediated T cell proliferation is regulated by Herpes Virus Entry Mediator costimulatory molecule.2014
Author(s)
Ando, Y., Yasuoka, C., Mishima, T., Ikematsu, T., Uede, T., Matsunaga, T. and Inobe, M.
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Journal Title
In Vitro Cell. Dev. Biol.- Animal
Volume: 50
Issue: 4
Pages: 313-320
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Proteasome inhibitors and knockdown of SMG1 cause accumulation of Upf1 and Upf2 in human cells.2014
Author(s)
Zhao, X., Nogawa, A., Matsunaga, T., Takegami, T., Nakagawa, H. and Ishigaki, Y.
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Journal Title
Int. J. Oncol.
Volume: 44
Issue: 1
Pages: 222-228
DOI
Related Report
Peer Reviewed
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[Presentation] NER-dependent DSB formation activates ATM signaling pathway in mammalian quiescent cells2015
Author(s)
Wakasugi, M., Sasaki, T., Nagaoka, M., Matsumoto, M., Inoue, K., Horibata, K., Tanaka, K. and Matsunaga, T.
Organizer
Keystone Symposia “Genomic instability and DNA repair joint with DNA replication and recombination”
Place of Presentation
Whistler Conference Centre (Whistler, Canada)
Year and Date
2015-03-01 – 2015-03-06
Related Report
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[Presentation] Newly developed immunoassay for evaluating nucleotide excision repair ability using individual peripheral lymphocytes and its possible application to the diagnosis of xeroderma pigmentosum2014
Author(s)
Honda, M., Nishiyama, C., Inobe, M., Wakasugi, M., Moriwaki, S. and Matsunaga, T.
Organizer
International Symposium on Xeroderma Pigmentosum and Related Diseases: Disorders of DNA Damage Response -Bench to Bedside-
Place of Presentation
神戸国際会議場（兵庫県神戸市）
Related Report
Invited
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