2014 Fiscal Year Final Research Report
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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| 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 |
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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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| Free Research Field |
分子細胞生物学
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