| Co-Investigator(Kenkyū-buntansha) |
MASUKATA Hisao Graduate School of Science, Osaka University, Professor, 大学院・理学研究科, 教授 (00199689)
SHINOMIYA Tomoyuki Mitsubishi Kase Institute of Life Sciences, Project Leader Scientist, 主任研究員
MATSUKAGE Akio Graduate School of Science, Japan Women's University, Professor, 理学部, 教授 (90019571)
SHIRAHIGE Katsuhiko Graduate School of Biological Sciences, Nara Advanced Institute of Science and Technology, Associate Professor, バイオサイエンス研究科, 助教授 (90273854)
MASAI Hisao Institute of Medical Science, University of Tokyo, Associate Professor, 医科学研究所・分子生物学研究部, 助教授 (40229349)
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| Research Abstract |
The ultimate goal of this research proposal is to understand the mechanisms of regulation of replication initiation in both prokaryotes and eukaryotes.
This research group has investigated three aspects of replication initiation ; the origin of replication, the components of replication initiation, and the regulation of initiation. During this research period, origin regions of replication were precisely analyzed in chromosomes of Schizosaccharomyces pombe, and Drosophila melanogaster. In Saccharomyces cerevisiae, the firing timing of every origins on a whole chromosome was thoroughly investigated, revealing the control mechanisms of initiation of DNA replication at chromosomal level. As to the components of replication initiation, homologues of proteins (ORC, MCM, Cdc45, etc.) essential for initiation of chromosome replication have been shown to be conserved in eukaryotic species. In particular, Cdc45 has been found to play a crucial role in the unwinding of origin DNA and recruiting DNA polymerase alpha onto the unwound DNA.As to the regulation of initiation, S-phase promoting kinases have been shown to play a universal role in the regulation of initiation through the phosphorylation of target proteins. With Drosophila melanogaster, two types of transcription factors have been shown to be involved in the trasncription of replication-related genes. Further, studies on regulatory mechanisms of replication initiation in E.coli reveals that the function of initiator protein is regulated by DNA polymerase.
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