Analysis of a novel molecular mechanism for decision of cell fate in response to DNA damage
Project/Area Number |
22681006
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Risk sciences of radiation/Chemicals
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Research Institution | Kobe University |
Principal Investigator |
SAKAI Wataru 神戸大学, 自然科学系先端融合研究環バイオシグナル研究センター, 助教 (70526251)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2012: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
|
Keywords | ファンコニ貧血 / アポトーシス / DNA損傷応答 / FANCD2 / カスパーゼ |
Research Abstract |
FANCD2is one ofthe responsiblegenes for a rare genetic disorder, Fanconi anemia syndrome. Many researchers reported that FANCD2 protein is a key factor for DNA interstrand crosslink repair. In the pilot study, I found a novel phenomenon that the FANCD2 protein was cleaved into atleast four smaller fragments when cells were treated with relatively high doses of genotoxic agents. In vitro and in vivo analyses showed that the DNA damage-induced cleavage of FANCD2 was dependent on caspase-3. All the cleavage sites were identified and the mutant FANCD2 protein lacking those cleavage sites was generated. When the non-cleavable mutant FANCD2 protein was stably expressed in a FANCD2-deficient cell line, the cells showed resistance to genotoxic agents compared with the cell line expressed wild-type FANCD2 protein. In the absence of exogenous genotoxic stress, however, only cell line expressed wild-type FANCD2 showed significant resistance to apoptosis induction by caspase-8 activation. All these results implied the possibility that FANCD2 contributes to regulate apoptosis induction negatively independent of DNA repair response.
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Report
(4 results)
Research Products
(17 results)