Study of mechanisms that decrease speed of replication fork progression in DNA damage response
Project/Area Number |
25440009
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Molecular biology
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Research Institution | Nara Institute of Science and Technology |
Principal Investigator |
Akiyama Masahiro 奈良先端科学技術大学院大学, バイオサイエンス研究科, 准教授 (80273837)
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Co-Investigator(Renkei-kenkyūsha) |
Maki Hisaji 奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (20199649)
Katayama Tsutomu 九州大学, 薬学研究科(研究院), 教授 (70264059)
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Project Period (FY) |
2013-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | DNA複製 / 複製フォーク / DNA損傷応答 / SOS応答 / 一分子解析 / DNAコーミング / DNAポリメラーゼ / DNA組換え酵素 / DNA複製フォーク / DNA複製速度 / 突然変異 / DNA組み換え酵素 / 分子マシナリー / レプリソーム / チェックポイント / 複製装置 |
Outline of Final Research Achievements |
When replication fork progression is aberrant, genome becomes instable by replication stress, leading to pathological disorders. Thus, the DNA damage response ensures genomic stability under replication stress. However, the dynamics of fork movements in cells and impact of the damage response on the dynamics remains unknown in any organism. To approach these problems in Escherichia coli cells, I had developed a new technique to accurately measure fork speed in the cells. Here, using the technique, we found that speed distribution of individual forks is relatively uniform but contains three subpopulations that have different speeds. A major determinant of fork speed was DNA polymerase (Pol) III in the replication machinery. Furthermore, onset of the DNA damage response uniformly decreased speed of individual forks. The slowdown mechanism was operated by detachment of the major speed determinant, Pol III, from forks by DinB (pol IV), and a noble function of RecA recombinase.
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Report
(5 results)
Research Products
(25 results)
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[Presentation] A single molecule approach to DNA replication in Escherichia coli cells demonstrated that DNA polymerae III is a major determinant of fork speed2014
Author(s)
Pham, TM., Tan, K.W., Sakumura, Y., Okumura,K., Furukohri, A., Maki, H.,and Akiyama, T.M.
Organizer
The 9th 3R International Symposium
Place of Presentation
御殿場高原ホテル(静岡県、御殿場市)
Year and Date
2014-11-11 – 2014-11-21
Related Report
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[Presentation] Escherichia coli DNA polymerase IV mediates quick recpovery of repliaction forks stalled at N2-dG adducts.2014
Author(s)
Furukohri, A., Ikead, M., Akiyama, M., Katayama, T., Fuchs R.P., and Maki, H.
Organizer
The 9th 3R International Symposium
Place of Presentation
御殿場高原ホテル(静岡県、御殿場市)
Year and Date
2014-11-11 – 2014-11-21
Related Report
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[Presentation] A single molecule approach to DNA replication in Escherichia coli cells demonstrated that DNA polymerae III is a major determinant of fork speed2014
Author(s)
Pham, TM., Tan, K.W., Sakumura, Y., Okumura,K., Furukohri, A., Maki, H.,and Akiyama, T.M.
Organizer
DNA polymerases: Biology, Diseases and Biomediacal Appliatiuon Conference 2014
Place of Presentation
Robinson collage (Cambridge, England)
Year and Date
2014-08-31 – 2014-09-04
Related Report
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[Presentation] Escherichia coli DNA polymerase IV mediates quick recpovery of repliaction forks stalled at N2-dG adducts2014
Author(s)
Furukohri, A., Ikead, M., Akiyama, M., Katayama, T., Fuchs R.P., and Maki, H.
Organizer
DNA polymerases: Biology, Diseases and Biomediacal Appliatiuon Conference 2014
Place of Presentation
Robinson collage (Cambridge, England)
Year and Date
2014-08-31 – 2014-09-04
Related Report
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