2013 Fiscal Year Final Research Report
Novel mechanisms for eliminating oxidatively damaged RNA
| Project/Area Number |
24657006
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Genetics/Genome dynamics
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| Research Institution | Fukuoka Dental College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SEKIGUCHI Takeshi 九州大学, 医学系研究科, 助教 (60187846)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | RNA / 酸化 / 遺伝子発現 / タンパク質 / 発現異常 / 酸化グアニン / 酵素 / ストレス |
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| Research Abstract |
Reactive oxygen species are produced as side products of oxygen utilization and can lead to the oxidation of nucleic acids and their precursor nucleotides. Among the various oxidized bases, 8-oxo-7,8-dihydroguanine seems to be the most critical during the transfer of genetic information because it can pair with both cytosine and adenine. During the de novo synthesis of guanine nucleotides, guanylate kinase hardly acts on an oxidized form of GMP (8-oxo-GMP) formed by the oxidation of GMP or by the cleavage of 8-oxo-GDP and 8-oxo-GTP by MutT protein. The 8-oxo-GTP produced in this way and by the oxidation of GTP can be used for RNA synthesis. This misincorporation is prevented by MutT protein, which has the potential to cleave 8-oxo-GTP as well as 8-oxo-GDP to 8-oxo-GMP. When (14)C-labeled 8-oxo-GTP was applied to CaCl2-permeabilized cells of a mutT(-) mutant strain, it could be incorporated into RNA at 4% of the rate for GTP.
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[Journal Article] Age-dependent increasers in the oxidative damage of DNA, RNA, and their metabolites in normal and senescence-accelerated mice analyzed by LC-MS/MS : Urinary 8-oxoguanine as a novel biomarker of aging2012
Author(s)
Wei Gan, Ben Nie, Fei Shi, Xin-Min Xu, Chan Qian, Yasumitsu Takagi, Hiroshi Hayakawa, Mutuo Sekiguchi, Jian-Ping Cai
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Journal Title
Free Radical Biology and Medicine
Volume: 52
Pages: 1700-1707
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