Researchers discover new complex proteins that control the separation of chromosomes

Researchers discover new complex proteins that control the separation of chromosomes

A new protein complex regulating Aurora B localization is identified by researchers from the university in Tsukuba to ensure chromosomes are properly separated during cell division.

It is no secret that DNA is a building block of life in the form of chromosomes. Incorrect chromosome distribution during cell division can be catastrophic.

Copy or aneuploidy of unbalanced chromosomes is a hallmark of tumours that affect the development and survival of all organisms, including humans.

Cells have fascinated researchers over the centuries how genetic material is disseminated. Researchers at Tsukuba University led by KeijiKimura as associate professor identified a new protein complex, NWC, involved in the distribution of chromosomes in a study published in June 2020 in Nucleic Acids Research.

NWC is related to a membrane-less intranuclear design, the nucleolus, which relocates during cell division to the periphery of chromosomes.

Researchers discover new complex proteins that control the separation of chromosomes
NOL11 depletion disrupts sister chromatid cohesion. (A) Defect in sister chromatid cohesion by NOL11 depletion. Mitotic chromosome spreads were prepared from HeLa cells transfected with siCont. or siNOL11 and stained with Giemsa stain. (Left) Typical examples of normal (top), loss of primary constriction (middle), or single chromosomes (bottom), respectively. Scale bar, 2 μm. (Right) Percentages of normal and aberrant chromosomes. (B) Delocalisation of Sgo1 from centromeres. HeLa cells transfected with siCont. or siNOL11 were fixed with 4% PFA after pre-extraction and co-stained with anti-Sgo1 (left, green) and anti-CENP-A (right, green) and ACA antibodies (red) and then DAPI (blue). Representative cells are shown. Scale bar, 2 μm.

Three different proteins are contained in the protein complex: NOL11, WDR43 and Cirhin. The nucleolus is usually associated with NOL11, with the WD-repeat protectins WDR43 and Cirhin.

“This study is important because the mythical functions of nucleolar proteins have to date been largely uncharacterized,” says Kimura.

The team investigated the location of NOL11 by immunofluorescence in human cells. The protein location can be visualized by means of a specialized microscope by means of its “glow.”

They found that during mitosis or nuclear division, NOL11 was located on the periphery of chromosomes.

When we examined the NOL11 protein we realized that it lacked any functional motifs. We then explored the idea that perhaps it functions in a complex with other proteins.”

Keiji Kimura, Associate Professor, University of Tsukuba

The research team has identified and characterized the NWC complex using advanced molecular techniques.

They looked at individual protein removal effects from the complex and found that NWC needs all three components to locate chromosome and function in mitosis.

Reducing cell NWCs led to an incomplete progression from the cell cycle by failing to separation, misalignment, and defects of locations of proteins, including Aurora B, the cohesin complex, and histone H3 phosphorylation, required for accurate chromosome distribution.

The findings presented by Associate Professor Kimura and colleagues show that NWC functions specifically in the stability of mitotic chromosomes through the accumulation of Aurora B at the centroms, partly through histone phosphorylation regulations.

It remains to be determined exactly how NWC controls histone phosphorylation close to centromers.

Giving correct chromosome dissemination a new focus on genes which result in aneuploidy or unequalled chromosome copies when mutated is critically important in the furtherance of life and disease prevention.

Source:

University of TsukubaJournal reference:

Fujimura, A., et al. (2020) Identification of a novel nucleolar protein complex required for mitotic chromosome segregation through a centromeric accumulation of Aurora B. Nucleic Acids Researchdoi.org/10.1093/nar/gkaa449.

Researchers discover new complex proteins that control the separation of chromosomes

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