Scientists discover a mechanism that shapes the distribution of centromeres

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Since the 1800s, scientists have noted the configuration of centromeres, a special chromosomal region that is vital for cell division, in the nucleus. Until now, however, the determining mechanisms and biological significance of centromere distribution have been poorly understood. A team led by researchers from the University of Tokyo and their collaborators recently proposed a two-step regulatory mechanism that shapes the distribution of centromeres. Their findings also suggest that the configuration of the centromere in the nucleus plays a role in maintaining genome integrity.

The results were published in natural plants.

During the process of cell division, special chromosomal domains called centromeres are pulled to opposite ends of the cell. After cell division is completed and the cell nucleus is built, the centromeres are spatially distributed within the nucleus. If the distribution of centromeres pulled towards both poles remains unchanged, the cell nucleus will have centromeres clustered on only one side of the nucleus. This uneven distribution of centromeres is called the Rabl configuration, after the 19th century cytologist Carl Rabl. The nuclei of some species instead show a scattered distribution of centromeres, known as the non-Rabl configuration.

“The biological function and molecular mechanism of the Rabl or non-Rabl configuration has been a mystery through the centuries,” said corresponding author Sachihiro Matsunaga, a professor at the Graduate School of Frontier Sciences at the University of Tokyo. “We succeeded in revealing the molecular mechanism to construct the non-Rabl configuration.”

Researchers studied the plant Arabidopsis thaliana, also known as Thale’s watercress and a specimen known to have a non-Rabl configuration, and its mutant form which had a Rabl configuration. Through their work, they discovered that the protein complexes known as condensin II (CII) and the protein complexes known as the nucleoskeletal and cotoskeletal binding complex (LINC) work together to determine the distribution of centromeres during cell division.

“The centromere distribution for the non-Rabl configuration is independently regulated by the CII-LINC complex and a nuclear lamina protein known as CROWDED NUCLEI (CRWN),” Matsunaga said.

The first step in the two-step regulatory mechanism of centromere distribution that the researchers discovered was that the CII-LINC complex mediates the diffusion of centromeres from late anaphase to telophase – two phases at the end of cell division. The second step in the process is that the CRWNs stabilize the centromeres scattered on the nuclear lamina inside the nucleus.

Then, to explore the biological significance, the researchers analyzed gene expression in A. thaliana and in its structure mutant Rabl. Because a change in the spatial arrangement of centromeres also changes the spatial arrangement of genes, the researchers expected to find differences in gene expression, but this assumption turned out to be incorrect. However, when the stress of DNA damage was applied, the mutant grew organs at a slower rate than the normal plant.

“This suggests that fine control of the spatial arrangement of centromeres is necessary for organ growth in response to DNA damage stress, and there is no difference in tolerance to DNA damage stress. DNA between non-Rabl and Rabl organisms,” Matsunaga said. “This suggests that the proper spatial arrangement of DNA in the nucleus, regardless of Rabl configuration, is important for the stress response.”

According to Matsunaga, the next steps are to identify the energy source that alters the spatial arrangement of specific DNA regions and the mechanism that recognizes specific DNA.

“Such findings will lead to the development of technology to artificially arrange DNA in the cell nucleus into an appropriate spatial arrangement,” he said. “This technology is expected to create stress-resistant organisms, as well as confer new properties and functions by altering the spatial arrangement of DNA rather than altering its nucleotide sequence.”

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Materials provided by University of Tokyo. Note: Content may be edited for style and length.

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