General principle and importance of organization of chromosome structures during mammalian development and cell differentiation
Project/Area Number |
22380188
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Applied molecular and cellular biology
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Research Institution | Mie University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
SUGIMURA Kazuto 三重大学, 大学院・医学系研究科, 助教 (90452226)
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Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
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Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2010: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
|
Keywords | 染色体 / ゲノム / 複製フォーク / クロマチン / エピジェネティクス / DNAメチル化 / DNA損傷 / クロマチン構造 / DNA複製 / DNAのメチル化 / 5-aza-2'-deoxycytidine |
Research Abstract |
In mammals, DNA methylation is an important epigenetic mark that is associated with chromosome construction. Using a DNA methylation inhibitor, we found that reduced levels of DNA methylation were associated with the activation of transcription from centromere regionsand a shift in replication timing of the pericenromeric regions from middle/late S to early S phase through depositing histone H3.3 on pericenromeric heterochromatin prior to the accumulation of the euchromatic histone modification, suggesting that DNA methylation is essential for proper organization of pericentromeric heterochromatin in differentiated mouse cells. We also found that DNA methyltransferase 1 knockdown or inhibition causes replication fork stalling and replication-associated DNA damages. We propose that replication stress in the course of passive DNA demethylation could be a source of spontaneous mutations and genomic instability during tumorigenesis and aging.
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] The histone chaperone FACT maintains replication fork rates2011
Author(s)
T.Abe, K.Sugimura, Y.Hosono, Y.Takami, M.Akita, A.Yoshimura, S.Tada, T.Nakayama, H.Murofushi, K.Okumura, S.Takeda, M.Horikoshi, M.Seki & T.Enomoto
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Journal Title
J.Biol.Chem.
Volume: 286
Issue: 35
Pages: 30504-30512
DOI
Related Report
Peer Reviewed
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