| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Shunichi Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (60188191)
TAKEYASU Kunio Kyoto University, Graduate School of Biostudies, Professor, 生命科学研究科, 教授 (40135695)
ISHIKAWA Fuyuki Kyoto University, Graduate School of Biostudies, Professor, 生命科学研究科, 教授 (30184493)
MATSUMOTO Tomohiro Kyoto University, Radiation Biology Center, Professor, 放射線生物研究センター, 教授 (80212223)
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| Research Abstract |
The aim of this COE research team is to understand the mechanisms that maintain chromosome integrity and accurately transmit chromosomes to daughter cells during mitosis. The mechanisms include the following areas of cell biology: (1) DNA replication, (2) cohesion between two sister chromatids, (3) chromosome condensation, (4) formation of the spindle body from centrosomes, (5) attachment of spindles to kinetochore, and the spindle checkpoint that monitors this attachment, (6) destruction of cohesion at the transition from metaphase to anaphase, (7) DNA repair and recombination, and (8) maintenance of telomeres. Since these cellular mechanisms are involved in the maintenance of chromosomal integrity, and are highly conserved between yeast and mammalian cells, extremely rapid progression of yeast genetic studies has been a driving force for our understanding of higher eukaryotic cell biology. Moreover, two complementary approaches were used for this investigation, namely genetics of fis
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sion yeast, and biochemical characterization as well as purification of proteins. The combination of these two methods allows an in depth analysis of biological problems and has a very high educational value for students enrolled in our COE research team.
By screening yeast mutants as well as determining components in purified kinetochore complex, Prof. Yanagida's group successfully identified several molecules present in the kinetochore, which are conserved from fission yeast to mammals. This group previously reported a number of findings about the role of cohesin and condensing complexes in mitosis, and reveals a novel function for these complexes during DNA repair in interphase nuclei. This finding also provides insight in the function of these complexes in mammalian cells, because both complexes are expressed in resting cells as well as mitotic cells in mammalian tissues. The major work of the other COE members are as follows : the molecular mechanism of polo-like kinase for triggering M phase (Prof. Nishida), the molecular switch to inhibit the spindle checkpoint and initiate anaphase (Prof. Matsumoto), the establishment of in vitro replication of telomeric sequences in Xenopus egg extract (Prof. Ishikawa), the development of new methods to observe chromatin structure using the atomic force microscopy (Prof. Takeyasu), and the comprehensive functional analysis of homologous recombination factors by a reverse genetic study of the chicken DT40 B lymphocyte line (Prof. Takeda). Prof. Takeda's laboratory also successfully established an experimental system for gene disruption in the Medaka fish
The publication record shows outstanding performance of this COE research group. Our studies will contribute to the understanding of carcinogenesis because compromised chromosome maintenance may result in a dramatic increase in the rate of mutations. Furthermore, our study will facilitate the development of cancer therapy, because radiotherapy and some of the chemotherapy such as cisplatin and taxol kills cycling cells by interfering DNA replication and spindle formation during the M phase. Less
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