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 - Radiation Biology Center
Radiation System Biology (Laboratory of Genome Maintenance)
Chromosomal DNA, a carrier of the blue print of life, must be faithfully duplicated and equally delivered to two daughter cells. Cells with extra chromosomes or less chromosomes (aneuploids), which are generated through unequal segregation of chromosomes, are a primary cause of genetic diseases such as Down syndrome. They have a great impact on tumor development/progression as well. We study mechanisms required for equal segregation of chromosomes with yeast and cultured human cells as major research materials.

  Tomohiro Matsumoto, Ph.D.
Professor
Research and Education
A series of the biochemical reactions necessary for self-duplication of life are orderly programmed in the cell cycle. In particular, most of the reactions, which are initiated once and only once at a specific stage of the cell cycle (such as DNA replication and segregation), are triggered by the completion of the preceding reaction. It is generally accepted that negative feedback loops (so called checkpoints) are responsible for suppression of the onset of a reaction until the completion of the preceding reaction. That sister chromatid separation must follow the completion of attachment of the spindle to all kinetochores is an important rule for equal segregation of chromosomes. The spindle checkpoint, our major research subject, is a surveillance mechanism to regulate cellular apparatus for compliance with this rule. It is a unique negative feedback that converts/amplifies a physical signal sensed by kinetochores (attachment of the spindle and/or tension) and regulates the timing of the sister chromatid separation. Mad2, a signal carrier of this feedback, plays a vital role in the spindle checkpoint. It is specifically localized at unattached kinetochores that are the origin of the checkpoint signal. Mad2 targets CDC20 and inhibits its activity to promote sister chromatid separation. We study Mad2, a central player of the spindle checkpoint, to reveal mechanisms, which regulate the activity of Mad2.


Radiation System Biology
Radiation Biology Center
Professor Tomohiro Matsumoto
Assistant
 Professor


Toshiyuki Habu
TEL +81-75-753-7552
FAX +81-75-753-7564
e-mail tmatsumohouse.rbc.kyoto-u.ac.jp
URL http://www.rbc.kyoto-u.ac.jp/
Sister chromatid separation at the onset of anaphase. Chromosomes (red) and the spindle (green) were stained with fluorescence.
Distribution of Mad2 at prophase. Nuclear membrane (red), Mad2 (green) and chromosomal DNA (blue) were stained with fluorescence.
Staffs
Recent Publications
1. Guohong Xia, Xuelian Luo, Toshiyuki Habu, Josep Rizo, Tomohiro Matsumoto, and Hongtao Yu (2004) Conformation-specific binding of p31comet to Mad2 antagonizes the function of Mad2 in the spindle checkpoint. EMBO J. 23:3133-3143.
2. Luo X., Tang Z., Xia, G., Wassmann K., Matsumoto T., Rizo, J. and Yu H. (2004) The Mad2 spindle checkpoint protein has two distinct natuively folded states. Nat Struct Mol Biol. 11:338-345.
3. Habu, T., Kim, S. H., Weinstein, J., and Matsumoto, T. (2002). Identification of a Mad2-binding protein, Cmt2, and its role in mitosis. EMBO J. 21: 6419-6428.
4. Kim, S. H., Lin, D. P., Matsumoto, S., Kitazono, A. and Matsumoto, T. (1998). Fission yeast Slp1: An effector of the Mad2-dependent spindle checkpoint. Science 279:1045-1047.