| Project/Area Number |
21689010
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Nagoya City University |
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Principal Investigator |
SHIMADA Midori Nagoya City University, 大学院・医学研究科, 講師 (60444981)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥28,080,000 (Direct Cost: ¥21,600,000、Indirect Cost: ¥6,480,000)
Fiscal Year 2010: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2009: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
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| Keywords | 細胞周期 / DNA損傷 / チェックポイント / クロマチン |
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| Research Abstract |
Transcriptional repression of E2F1 target genes is regulated by rapid reduction of histone H3-T11 phosphorylation, which is mediated at least in part by DNA damage induced Chk1 dissociation from chromatin. However, molecular mechanism(s) how this dephosphorylation triggers transcriptional repression remains elusive. Here, we identify an 'acetyl/phospho' cassette at H3-K9/T11 on E2F promoters, which is switched by replacement of Chk1-GCN5 complexes with protein phosphatase 1 (PP1)-HDACs complexes scaffolded on Rb-family pocket proteins. PP1 activity toward T11 dephosphorylation is regulated by Cdk1-dependent phosphorylation of PP1 at T311. Under unperturbed condition, Chk1/GCN5 complex existed on E2F1 promoters. After DNA damage, PP1/HADCs complex on pRb was recruited to E2F1. Our results thus suggest that T11 phosphorylation may function as a phospho-acceptor targeted by ATR-Chk1 axis and accelerate K9 acetylation, which is reversed by the activation of PP1 and recruitment of HDACs bound to Rb-related proteins by Chk1-dependent inhibition of Cdks after DNA damage.
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