This is a human cell preparing to divide. Over the course of an average life, the estimated 37 trillion cells in our body will regenerate by dividing about 50 to 70 times, each division forming two “daughter” cells that contain same number of chromosomes – 23 pairs – as the “mother” cell. Sometimes, though, the process goes wrong. Cancerous cells, for example, have abnormal numbers of chromosomes (known as aneuploidy). Down syndrome is caused by inheriting a single extra chromosome.
New research published in Nature Communications by scientists from Queen Mary University of London sheds light on the mechanisms that regulate the chromosomes being correctly pulled apart during cell division so that each new cell inherits a complete set. Using high-resolution microscopes to video the inner workings of live human cells, the team led by Viji Draviam has identified two proteins that work in balance to ensure the daughter cells have the correct number of chromosomes.
During cell division, Draviam explains, the mother cell’s DNA, wrapped up in the form of chromosomes, is divided into two equal sets by rope-like structures called microtubules that capture and pull apart the chromosomes at a special site called the kinetochore. The above image shows the microtubules in green, the chromosomes in blue and the kinetochore in red.
The two proteins – Aurora-B kinase and BubR1-bound PP2A phosphatase – are “tiny molecular machines” that enable the correct attachment between the chromosomes and microtubules. They act in opposition to each other, adding or removing phosphate groups respectively, to control the microtubules attaching to the chromosomes. “When these proteins don’t function properly, the cells can lose or gain a chromosome,” Draviam says. “This finding gives us a glimpse of an important step in the process of cell division.”
Draviam and her colleagues hope that understanding the role and balance of the proteins will lead to medical progress in preventing or treating aneuploidy. “By contributing to a molecular understanding of the chromosome segregation process,” she says, “this work will support future development of predictive markers or drug targets for a variety of disorders linked to irregular chromosome numbers.”
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