| Budget Amount *help |
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
PPM1D was originally identified as a p53-inducible Ser/Thr phosphatase. We have found that PPM1D-overexpressed cells often show “DNA bridge” which is one of chromosome segregation errors, however the mechanism remains obscure.
In this study, we showed that PPM1D overexpression induced DNA bridge in p53-independent manner. Co-immunoprecipitation analysis showed that PPM1D interacts with nuclear phosphorylated protein, TOP2A. Overexpressed PPM1D co-localized with endogenous TOP2A not only in the nucleus but also on the DNA bridge during anaphase in mitosis. Decatenation assay exhibited that overexpressed PPM1D suppresses the TOP2A activity. The phosphorylation analysis of TOP2A exhibited that overexpressed PPM1D induced the elevation of low level of phosphorylated-TOP2A. These data suggested that overexpression of PPM1D induces genome instability through the inhibition of TOP2A activity by the regulation of TOP2A phosphorylation level.
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