1999 Fiscal Year Final Research Report Summary
Studies on DNA-PK controlling cell functions (analysis of double-gene destruction with PARP)
| Project/Area Number |
10680665
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TERAODA Hirobumi Tokyo Medical and Dental University Medical Research Institute Professor, 難治疾患研究所, 教授 (30019137)
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| Project Period (FY) |
1998 – 1999
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| Keywords | knock-out mouse / DNA-dependent protein kinase / poly(ADP-ribose) polymerase / DNA repair / Ku protein / apoptosis |
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| Research Abstract |
The purpose of this research is to verify the hypothesis that DNA-dependent protein kinase (DNA-PK) exquisitely controls cell functions and cell fate. DNA-PK gene is responsible for mouse SCID defective in DNA end-joining process in V(D)J recombination and DNA double-strand break repair. Since several characteristics of DNA-PK are similar to those of poly(ADP-ribose) polymerase (PARP), the research focused on the relationship between them and complementarity to each other. PARP was phosphorylated by DNA-PK concomitantly with decrease in poly(ADP-ribosyl) action activity. At least in vitro, PARP stimulated DNA-PK activity as a DNA-binding regulatory component instead of Ku protein. Preparation of recombinant PARP of wild-type and truncated forms with individual and combined domains is now in progress. Although DNA-PK is not essential for cell survival, DNA-PK would subtly regulated DNA metabolism, including DNA replication, transcription, repair and recombination, for maintaining healthy life. In PARP-knock out (KO) mice, no severe dysfunction was observed except for lowering capacity of DNA repair. In order to analyze functional complementarity of DNA-PK and PARP, we intended to prepare double-gene KO mice and embryonic fibroblasts lacking both parp and DNA-PK genes. By mating scid+/-・PARP+/- mice, 129 males and 89 females were born. At present, no double-gene KO mice were obtained in genetially analyzed 51 mice of female. From 13.5-day embryos, primary cultured cells of fibloblasts lacking both parp and DNA-PK genes were obtained, out of which cell lines of embryonic fibloblast will be expected.
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Research Products
(12 results)
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[Publications] Teraoka, H.: "In Cell Cycle (in Japanese)"(ed. by Taya, Y., Nojima, H., and Hanaoka, F.), Yodosha, RNase H, p. 108-109 ; DNA ligase, p. 112-113 ; ATM/ATR, p. 138-139.. (1999)
Description
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