Scientists uncover mechanisms that shape the distribution of centromeres

Since the 1800s, scientists have noted the configuration of the centromere, a special region of chromosomes essential for cell division, in the nucleus. To date, however, the determination mechanism and biological significance of the centromere distribution is poorly understood. A team led by researchers from the University of Tokyo and their collaborators recently proposed a two-step regulatory mechanism that forms 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. Once the cell division is complete and the cell nucleus is built, the centromeres are distributed spatially in the nucleus. If the distribution of the centromeres drawn to the two poles remained unchanged, the cell nucleus would have centromeres clustered on only one side of the nucleus. This unequal distribution of centromeres is called the Rabl configuration, named after the 19th century cytologist Carl Rabl. The nuclei of some species instead exhibit a scattered distribution of centromeres, known as the non-Rabl configuration.

“The biological function and molecular mechanisms of Rabl or non-Rabl configurations have been a mystery for centuries,” said correspondent author Sachihiro Matsunaga, professor at the University of Tokyo’s Graduate School of Border Science. “We succeeded in unraveling the molecular mechanism for establishing a non-Rabl configuration.”

Researchers study plants Arabidopsis thaliana, also known as thale lettuce and specimens known to have a non-Rabl configuration, and its mutant form having a Rabl configuration. Through their work, they discovered that a protein complex known as condensin II (CII) and a protein complex known as the nucleoskeleton and cotoskeleton linker complex (LINC) work together to determine the distribution of centromeres during cell division.

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

The first step of the two-step regulation mechanism of centromere distribution discovered by the researchers was that the CII-LINC complex mediates centromere scattering from late anaphase to telophase — two phases at the end of cell division. The second step of this process is that CRWN stabilizes the centromeres scattered on the nuclear lamina within the nucleus.

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

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

According to Matsunaga, the next step is to identify the resources that alter the spatial makeup of specific DNA regions and the mechanisms that recognize specific DNA.

“The findings will lead to the development of technology to artificially arrange DNA within the cell nucleus in a suitable spatial arrangement,” he said. “It is hoped that this technology will make it possible to create stress-resistant organisms, as well as provide new properties and functions by altering the spatial makeup of DNA rather than editing its nucleotide sequence.”

Story Source:

Material provided by Tokyo University. Note: Content can be edited for style and length.

#Scientists #uncover #mechanisms #shape #distribution #centromeres