2003 Fiscal Year Final Research Report Summary
Oxidatively damaged DNA Repair and Its Related Enzymes
| Project/Area Number |
13480193
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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 |
Structural biochemistry
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| Research Institution | Osaka University |
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Principal Investigator |
KURAMITSU Seiki Osaka University, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (60153368)
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| Co-Investigator(Kenkyū-buntansha) |
MASUI Ryoji MASUI,Ryoji, 大学院・理学研究科, 講師 (40252580)
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| Project Period (FY) |
2001 – 2003
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| Keywords | DNA repair / damaged DNA / nucleotide / catalytic mechanism / substrate recognition / extreme thermophile |
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| Research Abstract |
DNA is oxidatively damaged by oxidative stress especially reactive oxygen species. Such damages result in mutations and cause a number of diseases including cancer. Among oxidatively damaged bases 8-oxoguanine can lead to increased frequency of G : C to T : A transversion. MutM is a base excision repair enzyme that recognize oxidatively damaged guanines including 8-oxoguanine. This enzyme catalyzes three reactions: excision of the 8-oxoguanine base (glycosylase activity). and b-and d-elimination of the resultant abasic site (AP-lyase activity), Recently, we also determined the structures of MutM-DNA complex. These structures suggest involvement of many amino acid residues in DNA-binding and catalytic activities. However, proposed roles of those residues have not been verified experimentally. To establish the detailed mechanism of MutM reaction, this study investigated functional roles of several amino acid residues in the catalysis. We selected several conserved residues based on the crystal structure of the complex and replaced them by other residues using site-directed mutagenesis. The obtained results demonstrate that some residues are involved in the catalytic reaction of MutM.
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[Publications] Hoseki, J., Okamoto, A., Takada, N., Suenaga, A., Funatsugi, N., Konagaya, A., Taiji, M., Yano, T., Kuramitsu, S., Kagamiyama, H.: "Increased Rigidity of Domain Structures Enhances the Stability of A Mutant Enzyme Created by Directed Evolution"Biochemistry. 41. 14469-14475 (2003)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yoshiba.S., Ooga.T., Nakagawa, N., Shibata.T., Inoue.Y., Yokoyama, S., Kuramitsu, S., Masui.R.: "Structural Insights into The Thermus thermophilus ADP-Ribose Pyrophosphates Mechanism via Crystal Strictures with The Bound Substrate and Metal"J.Biol.Chem.. (in press). (2004)
Description
「研究成果報告書概要(欧文)」より
