Formation and repair mechanisms of radiation-induced DNA-protein cross-links
| Project/Area Number |
18H03374
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 63020:Radiation influence-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
IDE Hiroshi 広島大学, 統合生命科学研究科(理), 教授 (30223126)
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| Co-Investigator(Kenkyū-buntansha) |
平山 亮一 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 重粒子線治療研究部, 主任研究員(定常) (90435701)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | 放射線 / DNA損傷 / 修復機構 |
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| Outline of Final Research Achievements |
DNA molecules that carry the genetic information of the cell are constantly associated with various proteins. DNA-associated proteins are covalently trapped in DNA to form DNA-protein cross-links (DPCs) when cells are irradiated with ionizing radiation or treated with other DNA-damaging agents. However, little is known about the amount of DPC damage resulting from the exposure to ionizing radiation and other DNA-damaging agents. Furthermore, how DPC damage is repaired in cells remains largely elusive. In the present study, we irradiated cells with X-rays and analyzed the proteins involved in DPCs. The possible mechanisms of DPC formation are discussed. We also used cells that were deficient in tyrosyl-DNA phosphodiesterases (TDP) 1 and 2 together with other enzymes, and elucidated the roles of these enzymes in the repair of DPCs that contained the cleavage complex of topoisomerases 1 and 2 (TOP1cc and TOP2cc).
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| Academic Significance and Societal Importance of the Research Achievements |
DNA-タンパク質架橋（DPC）は，放射線，紫外線，ホルムアルデヒドなどの変異原物質で誘発される主要なDNA損傷の一つである。本研究により，DPCの生成機構と修復機構の一端が明らかになった。DNA損傷は，発がんや老化の原因となることが知られていることから，DPC形成に起因する発がんおよび老化機構の解明につながると予想される。また，カンプトテシンやエトポシドなどの抗がん剤は，DPCを形成することによりがん細胞を死滅させる。DPC修復に関わる酵素を標的とした阻害剤を分子設計することにより，効果の高いがん治療が可能となるとなる。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Participation of TDP1 in the repair of formaldehyde-induced DNA-protein cross-links in chicken DT40 cells2020
Author(s)
Toshiaki Nakano, Mahmoud I. Shoulkamy, Masataka Tsuda, Hiroyuki Sasanuma, Kouji Hirota, Minoru Takata, Shin-ichiro Masunaga, Shunichi Takeda, Hiroshi Ide, Tadayoshi Bessho, Keizo Tano
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Journal Title
PLOS ONE
Volume: 15
Issue: 6
Pages: 0234859-0234859
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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