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Experimental Pathology

Overview

Loss or gain of chromosomes is associated with many cancer cells. This property, called chromosome instability, might arise from a lesion in the chromosome segregation machinery. In mitosis, chromatin is structurally reorganized into chromosomes in which replicated DNA molecules are seen as sister chromatids. Each chromosome is then captured by two opposing poles of the spindle which allows the segregation of sister chromatids towards opposite poles. Our ultimate goal is to understand how chromosomes condense, achieve bipolar spindle attachments and how cohesion is subsequently dissolved to allow sister chromatid separation. Elucidating these processes should provide insight into the mechanisms underlying chromosome instability in cancer cells.Original Web SiteNew Window

Projects

  1. How chromosomes are assembled in mitosis?
  2. How kinetochore-microtubule attachment is controlled?
  3. How do cells induce chromosome segregation at the correct time?
  4. Mechanisms of chromosomal instability in cancer cells

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Publications

Publications

Gallego-Paez, L.M., Tanaka, H., Bando, M., Takahashi, M., Nozaki, N., Nakato, R., Shirahige, K., Hirota, T.
Smc5/6-mediated replication progression contributes to chromosome assembly in human cells. .
Mol Biol Cell, in press (2013)
Shindo, N., Kumada, K., Hirota, T.
Separase-sensor reveals dual roles for separase coordinating cohesin cleavage and cdk1 inhibition.
Dev Cell, 23, 112-123 (2012)
*Abe, S., *Nagasaka, K., Hirayama, Y., Kozuka-Hata, H., Oyama, M., Aoyagi, Y., Obuse, C., Hirota, T., (*equal-contribution).
The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II.
Genes Dev, 25, 863-874 (2011)
Abe, Y., Okumura, E., Hosoya, T., Hirota, T.,* Kishimoto, T.* (*joint correspondence)
A single starfish Aurora kinase performs the combined functions of Aurora-A and Aurora-B in human cells.
J Cell Sci, 123, 3978-3988 (2010)
Uchida, K.S., Takagaki, K., Kumada, K., Hirayama, Y., Noda, T., Hirota, T.
Kinetochore stretching inactivates the spindle assembly checkpoint.
J Cell Biol, 184, 383-390 (2009)

Contact

Toru Hirota, M.D., Ph.D.
The Cancer Institute
Japanese Foundation for Cancer Research (JFCR)
Ariake 3-8-31, Koto-ku Tokyo, 135-8550
Tel. +81-3-3570-0446
E-mailFthirota@jfcr.or.jp

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