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Analysis of Structures of Protein Complexes Responsible for Equal Chromosome Segregation (Press Release)

Release Date
03 Feb, 2012
  • BL38B1 (Structural Biology III)
  • BL44XU (Macromolecular Assemblies)
-Providing insights into epigenetics of equal genome segregation-

Research Organization of Information and Systems,
National Institute of Genetics

Accurate cell division is essential for maintaining life. In cell division, DNA, which carries genomic information, is formed into a structure called the chromosome, which is then correctly replicated, doubled and equally segregated (Fig. 1). There is a specific region called the "centromere"*1 at the center of a chromosome. Approximately 100 types of protein are assembled in the centromere, where the genome is equally segregated. Although recent reports have suggested that the structure of the centromere of higher organisms is determined by a non-DNA-sequence-based mechanism (epigenetics*2), there are still questions about how so many proteins are assembled in the region that becomes the centromere. Tatsuya Nishino (Assistant Professor) and Tatsuo Fukagawa (Professor) and their colleagues at the Division of Molecular Genetics, National Institute of Genetics analyzed the crystal structure of the protein complexes bound to the centromere in a highly precise manner and found that this structure closely resembles that of histone,*3 which wraps DNA in place. These findings will provide new insights into the epigenetic control of the function of the centromere.

The findings of this study were published in the American scientific journal, Cell, on 3 February 2012.

"CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like folds"
Tatsuya Nishino, Kozo Takeuchi, Karen E. Gascoigne, Aussie Suzuki, Tetsuya Hori,Takuji Oyama, Kosuke Morikawa, Iain M. Cheeseman, and Tatsuo Fukagawa
Cell, 148, Issue 3, 487-501, 3 February 2012

*1 Centromere

The centromere is a chromosomal region to which spindle fibers are bound during cell division. The kinetochore consisting of DNA and proteins that exist in the centromere plays an essential role in chromosome segregation.

*2 Epigenetics
Generally, genetic information is transmitted to offspring in the form of a primary DNA sequence. If there are any changes in the primary DNA sequence, the changed genetic information is transmitted to the offspring, and thus mutations caused by those changes will be observed. However, sometimes mutations occur although there are no changes in the primary DNA sequence. Because these phenomena are caused by acquired modifications of DNA and the proteins bound to DNA, the study of such phenomena is called epigenetics, in contrast to genetics. Recently, epigenetics has been attracting attention following the completion of the sequencing of the human genome, and the focus of research has shifted to the mechanisms of the regulation of phenotypic expression.

*3 Histone
Histone is a basic protein found in eukaryotic chromosomes. It has a role in the storage of DNA, a very long molecule, in the cell nucleus. DNA is bound to histone in the cell nucleus.


Fig.1 Cell division and chromosome behavior during cell division
Fig. 1 Cell division and chromosome behavior during cell division

Inaccurate cell division leads to a faulty segregation of chromosomes, resulting in cancerous changes in cells. In normal cell division, chromosomes are equally segregated by spindle fibers, which extend from both poles of the cell, holding and pulling the centromere (central part) of the chromosomes.


Fig. 2 The structures of CENP-S-X and CENP-T-W resemble that of histone. Together they constitute CENP-T-W-S-X. Similarly to an ordinary histone that is wrapped by DNA, CENP-T-W-S-X is also wrapped by DNA and forms a unique structure (DNA-CENP-T-W-S-X structure). This structure acts as the core of a normal centromere structure. When CENP-S-X is deactivated, this structure cannot properly bind to DNA, and, thus, a normal centromere cannot be formed.

For more information, please contact:
 Professor. Tatsuo Fukagawa

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