Genome-wide identification of DNA replication origin sequences in human cells
| Project/Area Number |
16K12595
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | DNA複製 / 複製ポリメラーゼδ / 複製ポリメラーゼε / 複製起点 / シタラビン（Cytarabine） / 変異 / ヒト細胞 |
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| Outline of Final Research Achievements |
DNA replication is initiated from replication origin sequences in the genome. Although the locations of all origins have been identified in yeast species, the replication origins have not yet been mapped in the human genome. The aim of this research is to map all origin sequences in human cells, TK6 B cell line. DNA polymerases δ and ε (Polδ and Polε) play roles in lagging-strand and leading-strand replication, respectively. Prof. Tony Carr (Sussex, UK) mapped all replication origins in the yeast genome by determining the exact locations of polymerase switching during lagging and leading strand replication. We had followed this method, which used the Polδ and Polε mutants that frequently mis-incorporates ribonucleotides. We then learned that such mutant polymerases are highly cytotoxic to human cells. We have established another method, and already sent mutant cells to a collaborator, Prof. Carr in Sussex, UK. They will map all replication origin sequences in the near future.
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Report
(3 results)
Research Products
(8 results)
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[Journal Article] The dominant role of proofreading exonuclease activity of replicative polymerase ε in cellular tolerance to cytarabine (Ara-C).2017
Author(s)
Tsuda M, Terada K, Ooka M, Kobayashi K, Sasanuma H, Fujisawa R, Tsurimoto T, Yamamoto J, Iwai S, Kadoda K, Akagawa R, Huang SN, Pommier Y, Sale JE, Takeda S, Hirota K.
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Journal Title
Oncotarget
Volume: in press
Issue: 20
Pages: 33457-33474
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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