| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
MutM protein is a trifunctional DNA base excision repair enzyme, which removes oxidatively damaged bases and cleaves both the 3’- and 5’-phoshodiester bonds of the resulting apurinic/apyrimidinic site. The structures of the various complexes between a DNA glycosylase and same kinds of damaged DNA were reported. However, it remains to reveal the initial recognition mechanism of DNA glycosylases. To elucidate the initial recognition mechanism based on 3D structures, the complexes between of MutM and normal DNA or damaged DNA were crystallized and the structures of these complexes were determined. In the complex with damaged DNA, the DNA helix was sharply bent at the potion of the lesion and the 8-oxoguanine was flipped out of the DNA helix. In contrast, DNA bending and nucleotide flipping were not observed in the complex with the normal DNA. These results suggest that MutM searches lesions in an intact DNA helix at an initial recognition.
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