| Project/Area Number |
15K21771
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| Research Category |
Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Molecular biology
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| Research Institution | Tokai University |
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Principal Investigator |
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| Research Collaborator |
WATANABE Takaaki 東海大学, 医学部, 講師 (20421365)
ISHII Takamasa 東海大学, 医学部, 准教授 (20548680)
YAMASAKI Hiroyuki 東海大学, 医学部, 特定研究員 (90837816)
TANAKA Yukiko
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| Project Period (FY) |
2017 – 2019
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥57,200,000 (Direct Cost: ¥44,000,000、Indirect Cost: ¥13,200,000)
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| Keywords | DNA修復 / DNA損傷応答 / ファンコニ貧血 / 抗がん剤感受性 / リン酸化 / 癌 / DNA損傷･修復 / Fanconi anemia / シグナル伝達 / 分子生物学 |
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| Outline of Final Research Achievements |
Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure, cancer/leukemia susceptibility, developmental defects and cellular hypersensitivity to DNA interstrand crosslink (ICL)-inducing agents, such as cisplatin and mitomycin C. FA proteins and breast/ovarian cancer susceptibility proteins (BRCA1 and BRCA2) cooperate in a common pathway (the FA-BRCA pathway), which coordinates the repair of ICL lesions. Uncovering how this pathway is regulated is important for our understanding of basic cellular DNA repair/DNA damage response mechanisms, the molecular pathogenesis of FA and cancer as well as determination of sensitivity of cancer cells to ICL-inducing anti-cancer agents. In this study, we determined the mechanism(s) of regulation of the FA-BRCA pathway by phosphorylation/dephosphorylation of one of the FA proteins, FANCI and elucidated how a novel deubiquitinating enzyme, USP28, regulates the FA-BRCA pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
癌の治療には抗癌剤としてシスプラチンなどのDNA損傷剤がよく使われる。DNA損傷修復機構であるFanconi anemia-BRCA pathwayの異常がある癌細胞は、DNA損傷をうまく修復できないので、DNA損傷剤が効きやすい。したがって、我々の研究成果は、重要なDNA損傷修復機構の制御機構の解明に貢献するという学術的意義を持つとともに、日本人の死因の第一位を占める癌の治療法の改良にも貢献しうるという社会的意義を有する。
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