| Project/Area Number |
17590077
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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 |
Biological pharmacy
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| Research Institution | Setsunan University |
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Principal Investigator |
KAWASAKI Katsumi Setsunan University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (60177665)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Kenji Setsunan University, Faculty of Pharmaceutical Sciences, Research Associate, 薬学部, 助手 (30248067)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Genome stability / Drosophila melanogaster / RecQ / helicase / repair / nucleocapsid / retrotransposon / recombination |
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| Research Abstract |
1. RECQ5, possesses a short N-terminal region preceding the helicase domain and a long unique C-terminal domain. Although no disease has yet been genetically linked to a mutation in RECQ5, the prominent roles of RecQ helicase in the maintenance of genome stability suggest that RECQ5 helicase is likely to be important in vivo. To acquire a better understanding of RECQ5 function, we investigated protein interaction with the C-terminal domain of Drosophila melanogaster RECQ5/QE. A portion of Drosophila melanogaster retrotransposon mdg3, which corresponds to a nucleocapsid protein (gag-NC), was identified by use of the yeast two-hybrid system as interacting specifically with it. Glutathione S-transferase pull down experiments indicated that the mdg3 gag-NC bound mainly to an acidic region in the C-terminal domain of RECQ5/QE, which is adjacent to the RecQ helicase domain. The helicase activity of RECQ5/QE was stimulated by mdg3 gag-NC protein in vitro. These data suggest that RECQ5/QE helicase interacts physically and functionally with mdg3 gag-NC through the acidic region and that RecQ homologue might be involved in retrotransposition and genomic stability.
2. Members of the RecQ family of DNA helicases are involved in the cellular response to DNA damage and are regulated in the cell cycle. However, little is known about RecQ5, one of these members. The level of RECQ5/QE, Drosophila melanogaster RecQ5, was increased after the exposure of cultured cells to methyl-methanesulfonate. Transgenic flies that overexpressed RECQ5/QE in their developing eye primordia showed mild roughening of the ommatidial lattice. DNA-damaging agents and the mei-41 mutation enhanced the phenotype caused by RECQ5/QE over-expression. Over-expression of RECQ5/QE perturbed the progression of the cell cycle in response to DNA damage in the eye imaginal discs. These results suggest that RECQ5/QE interacts with components of the cell cycle during its progression in response to DNA damage.
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