Radiation Biology and Medicine I

kaoTomohiro Matsumoto Ph.D. Professor  btn

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.

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. We study some of players of the spindle checkpoint.
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Sister chromatid separation at the onset of anaphase. Chromosomes (red) and the spindle (green) were stained with fluorescence.r-077-2

Distribution of Mad2 at prophase. Nuclear membrane (red), Mad2 (green) and chromosomal DNA (blue) were stained with fluorescence.


Recent Publications

1.Horikoshi Y, Habu T, Matsumoto T. An E2 enzyme Ubc11 is required for ubiquitination of Slp1/Cdc20 and spindle checkpoint silencing in fission yeast. Cell Cycle. 12:961-71 (2013)
2.Ito D, Saito Y, Matsumoto T. Centromere-tethered Mps1 pombe homolog (Mph1) kinase is a sufficient marker for recruitment of the spindle checkpoint protein Bub1, but not Mad1. Proc Natl Acad Sci U S A. 109:209-14 (2012).
3.Iimori M, Ozaki K, Chikashige Y, Habu T, Hiraoka Y, Maki T, Hayashi I, Obuse C, Matsumoto T. A mutation of the fission yeast EB1 overcomes negative regulation by phosphorylation and stabilizes microtubules. Exp Cell Res. 318:262-75 (2012).
4.Habu, T., Kim, S. H., Weinstein, J., and Matsumoto, T. Identification of a MAD2-binding protein, Cmt2, and its role in mitosis. EMBO J. 21, 6419-6428 (2002).
5.Kim, S. H., Lin, D. P., Matsumoto, S., Kitazono, A. and Matsumoto, T. Fission yeast Slp1: An effector of the Mad2-dependent spindle checkpoint. Science 279, 1045-1047 (1998).

Laboratory

Professor : Tomohiro Matsumoto
Senior Lecturer : Kanji Furuya
TEL:+81-75-753-7552
FAX:+81-75-753-7564
e-mail:tmatsumo@house.rbc.kyoto-u.ac.jp
URL:http://www.rbc.kyoto-u.ac.jp/