| Budget Amount *help |
¥216,580,000 (Direct Cost: ¥166,600,000、Indirect Cost: ¥49,980,000)
Fiscal Year 2014: ¥38,740,000 (Direct Cost: ¥29,800,000、Indirect Cost: ¥8,940,000)
Fiscal Year 2013: ¥40,690,000 (Direct Cost: ¥31,300,000、Indirect Cost: ¥9,390,000)
Fiscal Year 2012: ¥40,560,000 (Direct Cost: ¥31,200,000、Indirect Cost: ¥9,360,000)
Fiscal Year 2011: ¥42,250,000 (Direct Cost: ¥32,500,000、Indirect Cost: ¥9,750,000)
Fiscal Year 2010: ¥54,340,000 (Direct Cost: ¥41,800,000、Indirect Cost: ¥12,540,000)
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| Outline of Final Research Achievements |
1. Molecular mechanisms underlying maintenance DNA methylation. Using Xenopus egg extracts, we successfully reproduced maintenance DNA methylation in vitro. Dnmt1 depletion resulted in a dramatic accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associated with ubiquitylated H3 in vitro. In mammalian cells, we also found Uhrf1-dependent uqibuityltion of H3 specifically during S phase. The RING finger mutant of Uhrf1 failed to recruit Dnmt1 to DNA replication sites and maintain DNA methylation in mammalian cultured cells.
2. Molecular mechanisms underlying senescence induction. Normal human diploid fibroblasts (HDFs) exposed to various senescence-inducing stimuli undergo a mitosis skip before entry into permanent cell cycle arrest. This mitosis skip is mediated by both p53-dependent premature activation of APC/CCdh1 and pRb family protein-dependent transcriptional suppression of mitotic regulators.
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