2016 Fiscal Year Final Research Report
Tumorigenesis by aberrant maintenance DNA methylation
| Project/Area Number |
26250027
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | The University of Tokyo (2016)
Nagoya City University (2014-2015) |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | DNAメチル化 / ゲノム不安定性 / DNA複製 |
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| Outline of Final Research Achievements |
Dnmt1 specifically binds to two mono ubiquitylated histone H3 such as H3K18Ub/K23/Ub, K14Ub/K18Ub, and K14Ub/K23Ub. The crystal structure of the replication foci targeting sequence (RFTS) of Dnmt1 in complex with H3-K18Ub/23Ub reveals striking differences to the previously identified ubiquitin-recognition structures.The binding of H3-K18Ub/23Ub results in spatial rearrangement of two lobes in the RFTS, suggesting the opening of its active site. Actually, incubation of Dnmt1 with H3-K18Ub/23Ub increases its catalytic activity in vitro. DNA hypomethylation by Dnmt1 knockdown results in an aberrant DNA replication program, leading to genomic instability.
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| Free Research Field |
分子腫瘍学
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