Scientists solve “a mystery of centuries”

Non-Rubble and Ruble Configurations

The upper panel shows the non-ruble configuration. Centromeres are scattered in the nucleus in green in magenta. The bottom panel shows the Rabble configuration. The nuclei are unevenly distributed in the nucleus. credit: Sachihiro Matsunaga, University of Tokyo

Biologists uncover mechanism that shapes centromere distribution.

Since the 1800s, scientists have paid attention to the configuration of the centromere, a special chromosomal region important for cell division, in the cell nucleus. However, until now, the fixation mechanism and the biological significance of centromere distribution were poorly understood. Recently, researchers proposed a two-step regulatory mechanism that shapes the centromere distribution. Their findings also indicate that the centromere configuration in the nucleus plays a role in maintaining genome integrity.

The results were published today (August 1, 2022) in the journal nature plants, The study was led by researchers from the University of Tokyo and their colleagues.

During the process of cell division special chromosomal domains called centromeres are pulled to opposite ends of the cell. After cell division is complete and the cell nucleus is formed, the nucleus is spatially distributed throughout the nucleus. If the distribution of the centromere drawn to the two poles remains unchanged, the cell nucleus will have grouped centromeres on only one side of the nucleus. This uneven distribution of the centromere is called the Rabble configuration after the 19th century cytologist Carl Rabble. The nuclei of some species instead show a diffuse distribution of the centromere. This is known as the non-rubber configuration.

“The biological function and molecular mechanism of the ruble or non-ruble configuration has been a mystery for centuries,” said corresponding author Sachihiro Matsunaga, a professor in the Graduate School of Frontier Sciences at the University of Tokyo. “We successfully uncovered the molecular mechanism for the creation of the non-Rubble configuration.”

centromere distribution in the root

Uneven distribution of the centromere (magenta) in the centromere (green). credit: Sachihiro Matsunaga, University of Tokyo

Scientists study plant Arabidopsis thaliana, also known as thal cress and a specimen known to have a non-rubl configuration, and its mutant form that had a rubl configuration. Through their work, they discovered that protein complexes known as condensin II (CII) and protein complexes known as linkers of the nucleoskeleton and cotoskeleton (LINC) play a role in determining centromere distribution during cell division. work together for.

“The centromere distribution for the non-rubber configuration is independently controlled by the CII-LINC complex and a nuclear lamina protein called a crowded nucleus (CRWN),” Matsunaga said.

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

Next, to ascertain the biological significance, the researchers analyzed gene expression. a. thaliana and in its ruble-structure mutant. Because a change in the spatial arrangement of the centromere also changes the spatial arrangement of genes, the researchers expected to find differences in gene expression, but this hypothesis turned out to be false. However, when DNA Damage stress was applied, mutant organs grew at a slower rate than the normal plant.

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

According to Matsunaga, the next step is to identify the power source that changes 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 in the appropriate spatial arrangement,” he said. “It is expected that this technology will make it possible to create stress-resistant organisms as well as confer new properties and functions by changing the spatial arrangement of the DNA rather than editing the nucleotide sequence of the DNA.”

Reference: “Two-Step Regulation of Centromere Distribution by Condensin II and Nuclear Envelope Proteins” by Takuya Sakamoto, Yuki Sakamoto, Stephen Grob, Daniel Slane, Tomo Yamashita, Nanami Ito, Yuka Oko, Tomoya Sugiyama, Takumi Higaki, Seichiro Hasezawa. Maho Tanaka, Akihiro Matsui, Motoki Seki, Takamasa Suzuki, Uli Grosniklaus and Sachihiro Matsunaga, August 1, 2022, nature plants,
DOI: 10.1038/s41477-022-01200-3

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