World's First Clarification of Crystal Structure of Human Chromosome Centromere at Atomic Resolution (Press Release)
- Release Date
- 11 Jul, 2011
- BL41XU (Structural Biology I)
- BL45XU (RIKEN Structural Biology I)
Waseda University
A group led by Hiroaki Tachiwana (Assistant Professor) and Hitoshi Kurumizaka (Professor) of the Faculty of Science and Engineering, Waseda University, has succeeded, for the first time in the world, in determining the crystal structure of the centromere, which is a structure at the center of human chromosomes. Since the awarding of the Nobel Prize in Physiology or Medicine to the scientists who clarified the structure of telomeres at the end of chromosomes in 2009, the structural clarification of centromeres had been attracting worldwide attention as the next key target in research. The achievement of this study is the world's first determination of the crystal structure of the human chromosome centromere at the atomic level, and is expected to provide an important clue to the clarification of the mechanisms underlying the development of hereditary diseases and carcinogenesis due to chromosome nondisjunction. The research results were published online in Nature on 11 July 2011. Publication: |
Human genomic DNA carrying genetic information is 2 m long and densely folded and stored in the cell nucleus with a diameter of only 5 µm. This folding structure of DNA is made possible by the structure of chromosomes, complexes of DNA and proteins. Condensed human chromosomes have a structure in which the centromere is narrow for cell division. When the centromere is drawn by spindle fibers during cell division, chromosomes are distributed evenly among two daughter cells and genetic information is accurately inherited by these daughter cells (Fig. 1). The inheritance of genetic information is essential for living organisms, which cannot live without the underlying formation of centromeres. Even when a centromere is formed, for humans, genetic information cannot be accurately inherited once a centromeric abnormality occurs, resulting in the development of diseases due to the abnormality in the number of chromosomes, such as Down syndrome, and the formation of cancer cells. Hence, the clarification of the mechanism unerlying the formation of centromeres has long been desired also for the purpose of clarifying the causes of such diseases.
Nucleosomes are the basic unit of chromosomes, in which DNA is wrapped twice around the histone octamer consisting of two each of four proteins called histones (H2A, H2B, H3, and H4), similarly to the form of a disc (Fig. 2). Centromeres have a special nucleosome structure, in which centromere protein A (CENP-A) replaces H3. Determining the crystal structure of a nucleosome containing CENP-A was expected to lead to the clarification of the mechanism of formation of centromeres.
In this study, the research group has succeeded, for the first time in the world, in determining the crystal structure of the human nucleosome containing CENP-A at the atomic level by X-ray crystallography using SPring-8 Structural Biology I (BL41XU) and SPring-8 RIKEN Structural Biology I (BL45XU). It was clarified that the nucleosome containing CENP-A has a structure different from that of the conventionally reported nucleosome containing H3 (Fig. 2).
These achievements will provide not only important information on the mechanism of formation of centromeres responsible for the accurate inheritance of genetic information, but also a clue to the clarification of the mechanism underlying the development of diseases due to abnormality in the number of chromosomes, such as Down syndrome, and the formation of cancer cells.
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