| Project/Area Number |
20590309
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
SUZUKI Motoshi Nagoya University, 大学院・医学系研究科, 講師 (80236017)
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| Co-Investigator(Kenkyū-buntansha) |
MURATE Takashi 名古屋大学, 医学部, 教授 (30239537)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | DNA複製 / ゲノムインスタビリティー / 癌 / DNA修復 / 細胞周期 / 肺癌 / チェックポイント / マイクロアレー / ヒストン修飾 / チェックポインイ |
|---|
| Research Abstract |
In examinations of 158 lung cancers and 5 mixtures of 10 normal lungs, cell cycle- and checkpoint-related genes generally showed mRNA expression increases in cancer, whereas POLD4 showed reduced mRNA in small cell lung cancer (SCLC). In the absence of POLD4, we observed defect in DNA repair activity, delay in cell cycle, and increased frequency of chromosomal break induction. Overexpression of an engineered POLD4 carrying silent mutations at the siRNA target site rescued these phenotypes, firmly establishing the role of POLD4 in these effects. In order to identify gene products that interact with POLD4, we performed an MS analysis using the immunoprecipitated protein fractions with POLD4, where ATM, CDC14 and other cell cycle checkpoint/progression proteins were detected. We further identified novel single nucleotide variations (SNV) in lung cancer cell lines. One of the SNV reduced the physical interaction ability with the catalytic subunit of pol delta. These results suggest that the newly identified SNV could be involved in the carcinogenesis by modifying DNA replication ability of DNA polymerase delta.
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