| Project/Area Number |
18390027
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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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| Research Field |
Biological pharmacy
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| Research Institution | Hiroshima University |
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Principal Investigator |
TAHARA Hidetoshi Hiroshima University, Graduate School of Biomedical Sciences, Professor (00271065)
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| Co-Investigator(Kenkyū-buntansha) |
SEIMIYA Hiroyuki The Cancer Institute of Japanese Foundation of Cancer Research, The Cancer Chemotherapy Center, Chief (50280623)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,660,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2007: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2006: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | telomere / G-tail / telomere binding protein / telomerase / anticancer drug / 老化 / 抗癌剤耐性 |
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| Research Abstract |
(1) Conditiona deletion of mouse Potla induces a DNA damage response at telomeres, resulting in p53-dependent replicative senescence. Potla-deficient cells exhibit overall telomere length and 3' overhang elongation as well as aberrant homologous recombination (HR) at telomeres, manifested as increased telomere sister chromatid exchanges and formation of telomere circles.
(2) We found that G-tail length were reduce in fibroblats, hetatocytes and HUVEC cells with cellular senescence. When forced expression of hTERT gene into these human normal cells, both telomere G-tail and total telomere length were elongated.
(3) The wild-type FN-tankyrase 1 increased the G-tail size to 134% of the mock cell line. FN-tank-ARC IVmut-ΔARC V also elongated the G-tail to 123% of the mock line. Collectively, reduced POT1 binding and increased G-tail length would reflect higher accessibility of telomerase to telomeres.
Further study of telomere associated proteins including shelterin complex (TRF1, TRF2, TIN2, PTOP, POT1, RAP1, Apollo) is important for the elucidation of genomic instability as well as genomic integrity in human disease such as cancer and aging.
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