Chromosome Dynamics Laboratory
Chief Scientist
Tatsuya HIRANO (Ph.D.)
The duplication and segregation of the genome are two of the most fundamental events in cell reproduction. Our laboratory is interested in understanding the molecular mechanisms that regulate the faithful segregation of chromosomes during mitosis. By using a cell-free extract derived from Xenopus laevis (African toad) eggs, we have discovered two multiprotein complexes, condensin and cohesin, that play central roles in chromosome condensation and sister chromatid cohesion, respectively. At the heart of the two complexes lie members of a large family of chromosomal ATPases, the SMC (structural maintenance of chromosomes) family. Accumulating lines of evidence suggest that SMC proteins actively participate in many aspects of higher-order chromosome dynamics, including chromosome-wide gene regulation, DNA recombination /repair and meiotic chromosome segregation. The long-term goal in our laboratory is to understand how condensin and cohesin work at a mechanistic level in vitro, and how they interact with other proteins to execute their essential functions in vivo. We take multidisciplinary approaches toward this goal, including biochemistry, cell biology, structural biology and biophysics. Our research will contribute to a better understanding of human health because chromosome anomalies, such as aneuploidy and translocations, are tightly associated with tumor development and birth defects.
- Chromosome architecture and segregation
- Molecular mechanisms of action of SMC protein complexes
- Chromosome dynamics and human disease
- December 03, 2010
- Unlocking the chromosome
- Lee, J., Hirano, T.:
"RAD21L, a novel cohesin subunit implicated in linking homologous chromosomes in mammalian meiosis"
J. Cell Biol. 192, 263-276 (2011) - Hirano, T.:
"How to separate entangled sisters: interplay between condensin and decatenase"
Proc. Natl. Acad. Sci. USA. 107, 18749-18750 (2010) - Shintomi, K., Hirano, T.:
"Sister chromatid resolution: a cohesin releasing network and beyond"
Chromosoma. 119, 459-467 (2010) - Shintomi, K., Hirano, T.:
"Releasing cohesin from chromosome arms in early mitosis: opposing actions of Wapl-Pds5 and Sgo1"
Genes Dev. 23, 2224-2236 (2009). - Onn, I., Aono, N., Hirano, M., Hirano, T.:
"Reconstitution and subunit geometry of human condensin complexes"
EMBO J. 26:1024-1034 (2007) - Gandhi, R., Gillespie, P. J., Hirano, T.:
"Human Wapl is a cohesin-binding protein that promotes sister chromatid resolution in mitotic prophase"
Curr. Biol. 16:2406-2417 (2006) - Hirano, M., Hirano, T.:
"Opening closed arms: long-distance activation of SMC ATPase by hinge-DNA interactions"
Mol. Cell. 21, 175-186 (2006) - Hirano, T.:
"At the heart of the chromosome: SMC proteins in action"
Nat. Rev. Mol. Cell Biol. 7, 311-322 (2006) - Losada, A. Hirano, T.:
"Dynamic molecular linkers of the genome: the first decade of SMC proteins"
Genes Dev. 19, 1269-1287 (2005) - Ono, T., Losada, A., Hirano, M., Myers, M. P., Neuwald, A. F., Hirano, T.:
"Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells"
Cell 115, 109-121 (2003)
Principal Investigator
- Tatsuya HIRANO
- Chief Scientist
Staff Scientist
- Katsuhiko KAMADA
- Senior Research Scientist
- Takao ONO
- Senior Research Scientist
- Kazuhisa KINOSHITA
- Senior Research Scientist
- Keishi SHINTOMI
- Research Scientist
Postdoctoral Fellow
- Daisuke YAMASHITA
- Special Postdoctoral Researcher
- Takayuki FUJIWARA
- Special Postdoctoral Researcher
- Kenji NISHIDE
- Postdoctoral Researcher
Technical Assistant
- Akiko MATSUURA
- Technical Staff II