| Budget Amount *help |
¥80,600,000 (Direct Cost: ¥62,000,000、Indirect Cost: ¥18,600,000)
Fiscal Year 2023: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2022: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2021: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2020: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2019: ¥22,620,000 (Direct Cost: ¥17,400,000、Indirect Cost: ¥5,220,000)
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| Outline of Final Research Achievements |
The aim of this study was to establish a structural basis for the replication of non-genome, especially DNA methylation and H3K9me3. Regarding H3K9me3, we established the preparation of ubiquitinated SETDB1, which is an enzymatically activated form. Cryo-EM analysis revealed a novel activation mechanism of the maintenance methyltransferase DNMT1 in DNA maintenance methylation. The structural basis for the inhibition of UHRF1 function by the maternal factor DPPA3 was elucidated using solution NMR. As a developmental study, a combination of computational science and structural biology was used to search for functional inhibitors of UHRF1, and compounds that inhibit binding to LIG1 were successfully identified. These findings led to the proposal of a novel regulatory mechanism for replication of the non-genome.
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