Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Research Abstract |
Thymine DNA glycosylase (TDG) is a base excision repair (BER) enzyme that interacts with the small ubiquitin-related modifier (SUMO)-targeted ubiquitin E3 ligase RNF4 and functions in the active DNA demethylation pathway. Here we found that the majority of TDG was SUMOylated in cells undergoing mitosis, while both SUMOylated and non-modified TDG were eliminated in cells arrested at S phase. In vitro and in vivo binding analyses revealed that TDG interacted with RNF4 in a SUMOylation-independent manner. In RNF4-depleted cells, both forms of TDG were efficiently degraded, suggesting that RNF4 was not the primary E3 ligase for controlling TDG stability. Our findings would not only be important for understanding posttranslational regulation of TDG but also provide implications for the TDG-RNF4 interaction in BER-driven active DNA demethylation during cell cycle progression.
|