Since the 1800s, scientists have noticed the configuration in the nucleus of centromeres, a special chromosomal region vital for cell division. However, until now, the determining mechanisms and biological significance of centromere distribution have not been sufficiently 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 indicate that the configuration of the centromere in the nucleus plays a role in maintaining genome integrity.
The results are published in Nature of Plants.
During cell division, special chromosomal domains called centromeres are pulled to opposite ends of the cell. After the completion of cell division and the construction of the cell nucleus, centrimeres are spatially distributed in the nucleus. If the distribution of centromeres contracted to the two poles remains the same, the cell nucleus will have centromeres clustered on only one side of the nucleus. This uneven distribution of centromeres is called the Rabelais configuration, after the 19th-century cytologist Karl Rabelais. The nuclei of some species show a dispersed distribution of centromeres, known as the non-Rabl configuration.
“The biological function and molecular mechanism of Rabl or non-Rabl configuration have been a mystery for centuries,” said corresponding author Sachihiro Matsunaga, a professor at the University of Tokyo’s Graduate School of Frontier Sciences. “We have successfully revealed the molecular mechanism for building a configuration unrelated to Rabl.”
Researchers studied the plant Arabidopsis thaliana, also known as tallow cress 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 protein complexes known as condensin II (CII) and protein complexes known as the linker nucleoskeleton-cataskeleton complex (LINC) work together to determine the distribution of centromeres during cell division.
“The distribution of centromeres for the non-Rabl-bound configuration is independently regulated by the CII-LINC complex and a nuclear plate 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 dispersal of centromeres from late anaphase to telophase, the two phases at the end of cell division. The second step in the process is that CRWNs stabilize the scattered centromeres at the nuclear plate in the nucleus.
Next, to examine the biological significance, the researchers analyzed the expression of genes in the A. Taliayan and it has a mutant rabble structure. Because changing the spatial arrangement of centromeres also changes the spatial arrangement of genes, the researchers expected to find differences in gene expression, but this hypothesis turned out to be incorrect. However, when DNA damage stress was applied, the mutant’s organs grew more slowly than the normal plant.
“This suggests that precise 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 between non-Rabl and Rabl organisms,” Matsunaga said. “This suggests that the appropriate spatial arrangement of DNA in the nucleus, independent of Rabl configuration, is important for the stress response.”
According to Matsunaga, the next steps are to determine the energy source that changes the spatial arrangement of certain DNA regions and the mechanism that recognizes certain DNA.
“Such findings will lead to the development of technology to artificially place DNA in the nucleus of a cell in the appropriate spatial arrangement,” he said. “This technology is expected to enable the creation of stress-resistant organisms, as well as confer new properties and functions by altering the spatial arrangement of DNA rather than editing its nucleotide sequence.”
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