Analysis of JET1 mutant, which does not require CDK activity in the initiation of DNA replication
| Project/Area Number |
18570167
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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 |
Molecular biology
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| Research Institution | National Institute of Genetics |
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Principal Investigator |
TANAKA Seiji National Institute of Genetics, Department of Cell Genetics, Assistant Professor (50263314)
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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 |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | DNA replication / CDK / cell cycle |
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| Research Abstract |
Eukaryotic DNA replication initiates from multiple origins of replication They are activated by two protein kinases, CDK and Cdc7-Dbf4, and DNA replication initiates in S phase. Substrates of CDK in this process was unknown for long time, S1d2 was shown as an essential target of CDK in the initiation in 2002. I have shown that Sld2 phosphorylation is necessary but not essential for the initiation. Therefore, to identify unknown CDK target, I set up a genetic screening. In the screening, phosphomimetic mutant of Sld2 (S1d2-D) was constructed and isolated the novel mutant JET1, which initiated DNA replication in conjunction with S1d2-D even in the absence of CDK activity. This JET1 mutation was occurred in CDC45, which required for the initiation and elongation. We revealed that Cdc45 is not the substrate of CDK, instead Sld3, the binding partner of Cdc45, is the essential target of CDK in initiation. We also showed that phosphorylations of Sld2 and Sld3 enhance the interaction Dpb11. It was suggested that this reaction triggers the initiation of DNA replication. Moreover by combining the mutations that bypass the phosphorylation of Sld2 and S1d3, we could bypass CDK requirements for initiation. These data strongly suggest that Sid2 and Sld3 constitute minimal essential requirements of CDK in initiation. These findings are crucial to understand the initiation reaction of eukaryotic DNA replication.
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Report
(3 results)
Research Products
(42 results)
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[Presentation] 複製開始因子の質的/量的制御2007
Author(s)
田中 誠司
Organizer
中部・東海DNA研究会
Place of Presentation
松本市,長野
Year and Date
2007-07-24
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] CDK-Mediated Regulation of Chromosomal DNA Replication in Budding Yeast.2006
Author(s)
Hiroyuki Araki, Seiji Tanaka, Yon-Soo Tak, Yoshimi Tanaka, Sachiko Muramatsu, Shizuko Endo, Toshiko Umemori, Kazuyuki Hirai, Yoichiro Kamimura
Organizer
Salk-Caltech-USC meeting_DNA Replication and Genome Integrity
Place of Presentation
San Diego, CA, USA
Year and Date
2006-08-10
Description
「研究成果報告書概要(欧文)」より
Related Report
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