2014 Fiscal Year Final Research Report
Structural Biology of Chromatin remodeling
| Project Area | Coupling of replication, repair and transcription, and their common mechanism of chromatin remodeling |
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| Project/Area Number |
22131007
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MORIOKA Hiroshi 熊本大学, 大学院生命科学研究部, 教授 (20230097)
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| Project Period (FY) |
2010-04-01 – 2015-03-31
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| Keywords | タンパク質 / クロマチンリモデリング / DNA合成酵素 / 構造生物学 / 時分割結晶学 |
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| Outline of Final Research Achievements |
Structural biology has played an important role in understanding mechanism of DNA repair or replication enzymes. However, structural bases for enzyme mechanisms through chromatin remodeling are not known. Furthermore, visualization of the catalytic reaction process at the atomic level remains unclear.
In this study, we have determined the crystal structure of one subunit in an ATP-dependent chromatin remodeling factor and suggested the overall shape combined with a lot of physicochemical, biochemical and molecular biological methods. The pathway of nucleotidyl transfer reaction by human DNA polymerase eta, a key enzyme in translesion synthesis in human cells was newly visualized using time-resolved protein crystallography by freeze trapping. In sequence, the substrate and two Mg ions are aligned, the nucleophile 3'-OH is deprotonated, the sugar conformation changes and the new bond is formed. An unexpected third Mg ion arrives with the new bond and stabilizes the intermediate state.
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| Free Research Field |
医歯薬学
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