| Project/Area Number |
13141204
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Nara Institute of Science and Technology |
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Principal Investigator |
UMEZU Keiko Nara Institute of Science and Technology, Graduate School of Biological Sciences, Assistant Professor, バイオサイエンス研究科, 助手 (20223612)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Takashi Osaka City University, Medical School, Professor, 大学院医学研究科, 教授 (70150349)
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| Project Period (FY) |
2001 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥41,700,000 (Direct Cost: ¥41,700,000)
Fiscal Year 2005: ¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2004: ¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 2003: ¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 2002: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2001: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | chromosome aberration / genome rearrangement / genetic recombination / DNA damage / DNA repair |
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| Research Abstract |
Our goal is to understand the molecular mechanisms of cellular processes that protect genome integrity against assaults arising endogenously. [Umezu] To understand the cellular processes involved in genome maintenance, we have developed an assay that analyzes the genetic events responsible for loss of a heterozygous marker (LOH) in yeast diploid cells. This assay allows the quantitative identification of various genetic alterations including chromosome loss, different types of chromosome rearrangements, and point mutations. By exploiting the molecular genetic systems to determine factors involved in genome maintenance, we showed that homologous recombination plays both positive and negative roles in the maintenance of genome stability. In other words, spontaneous DNA lesions capable of triggering homologous recombination occur at a strikingly high frequency throughout the genome during normal cell growth; the majority of lesions are processed precisely through sister chromatid recombination, and a part of the process leads to genetic alterations. We also found that homologous recombination is regulated at multiple steps in such a way as to suppress genome instability, presumably to control its dual roles. The focus of our current studies is on understanding how homologous recombination is regulated in a way to suppress genome instability and we are examining the effects of a defect in SGSJ, SRS2 or RDH54 on genome maintenance. The mutants have broader effects than expected from the previous studies, suggesting new roles of these genes in chromosome maintenance, which we are now investigating. [Morita] We have studied on mouse FDH1 gene, and showed that the gene product is expressed in testis germ cells, especially the cells in the pachytene stage where meiotic homologous recombination takes place. Now, we are investigating the effect of FDHp on the stability of various recombination proteins by RNAi method. We also under construction of FDH1 KO mouse.
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