| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Outline of Final Research Achievements |
DNA methylation of cytosine is a key epigenetic modification and crucial for normal development of mammals. DNA methylation patterns were maintained by Dnmt1. Mouse Dnmt1 is composed from multiple domains; the replication foci targeting sequence (RFTS), catalytic domain, and so on. From three-dimensional structure of mouse Dnmt1 lacking the N-terminal platform domain, a striking feature that the RFTS plugs the catalytic pocket is observed. Substrate DNA cannot gain access to the catalytic center unless the RFTS is removed from the catalytic pocket. Uhrf1 is reported to be a prerequisite factor. The SRA domain of Uhrf1 specifically recognizes hemi-methylated CpG.
In the present study, I have demonstrated that the direct interaction between the SRA of Uhrf1 and Dnmt1 contributes to the removal of the RFTS from the catalytic pocket to allow access of the substrate hemi-methylated DNA to the catalytic center. I elucidated one of the mechanisms to regulate maintenance methylation.
|
