The mysterious X in your cells
When your cells are about to divide, your genetic material folds into an X-shape. Why and how?
Summary
• The importance of the X-shape: When cells divide, DNA organizes itself into an X-shape. This structure is crucial for the correct distribution of genetic material and protects against damage during cell division.
• Breakthrough in understanding: Scientists have used advanced microscopy technology to study how DNA folds into the X-shape during cell division, which has long been a mystery.
• The role of condensin: The protein condensin, especially the variant condensin II, forms a network of DNA loops that contribute to folding and create the characteristic X-shape.
• Important progress: The study provides new insight into the mechanisms of cell division and may contribute to further research on chromosome organization, including how DNA structure affects gene expression.
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“This is a fundamental question that has remained unanswered in biology for a long time,” says Sandvold Beckwith, now an associate professor at the Department of Bioengineering at NTNU.
The question may simple, but it is not.
How does our genetic material organize itself into the important X-shape when cells are about to divide?
Sandvold Beckwith himself has been working on this particular question ever since he was a postdoctoral fellow at the European Molecular Biology Laboratory (EMBL) in Germany.
Other researchers have also looked into this question, and now their startling findings have been published in the prestigious journal Cell. Sandvold Beckwith is one of the first authors.
But to understand the significance of this finding, we need to look at the basics first.
The magic of DNA
The cells in your body contain genetic material called DNA. These DNA strands are what make you you, at least the biological part.
Kai Sandvold Beckwith. Photo: NTNU
This genetic material is distributed over a number of chromosomes. Humans have 23 pairs of DNA strands, for a total of 46 chromosomes.
Usually, the DNA strands lie in loose skeins, seemingly chaotic. But when the cells are about to divide and become two independent daughter cells, something happens that scientists have not yet been able to explain.
During cell division, the chromosomes arrange themselves in a compact X-shape. And there are good reasons why the chromosomes arrange themselves that way.
Why X is so important
“The characteristic X-shape is absolutely necessary for distributing the genetic material to the daughter cells,” Sandvold Beckwith says.
The X is simply an ideal shape for cell division. By forming this shape, the chromosome is divided into two so-called chromatids that are connected in the middle of the X. The shape largely prevents damage during the distribution of genetic material between the two daughter cells, such as if the DNA were to be left dangling when the last connection between the daughter cells is broken.
But none of this answers how the cells actually organize their normally loose DNA strands in this shape. This is what the smart guys in Sandvold Beckwith’s research group have figured out.
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Here’s how genetic material becomes Xs
“Using an advanced microscopy technology we recently developed, we were able to see right down to the nanoscale how the chromosomal DNA folds when the cells divide,” Sandvold Beckwith said.
This has previously been impossible because the DNA in the chromosomes is so tightly packed together. But the images with the new technique, together with computer simulations, allowed the researchers to make a breakthrough.
“It led us to a new model for how cells fold their chromosomes during cell division,” he said.
The key is a protein in the body called Condensin. Scientists already knew about this protein. It is found in several variants.
“Our model shows that cells create an overlapping and cross-linked network of loops in the DNA using Condensin,” he said.
The variant Condensin II is apparently particularly important because it helps to form very long loops. These long loops span large parts of the DNA, and therefore contribute greatly to folding.
“Distribution of the DNA loops, and the connections between them, causes the chromosomes to eventually form the characteristic X shape,” Sandvold Beckwith said.
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Important progress
The work began in collaboration with doctoral student Andreas Brunner when they both worked in the research group of Jan Ellenberg at EMBL in Heidelberg. The collaboration has continued since he became an associate professor at NTNU about a year ago.
“We believe this is a major and important advance in our understanding of cell division, one of the most fundamental phenomena in biology,” Sandvold Beckwith said.
The researchers have also been able to set up the new microscopy techniques at NTNU. This is done in collaboration with the Cellular & Molecular Imaging Core Facility (CMIC) at the Department of Clinical and Molecular Medicine. They are now using this to investigate other properties of chromosome organization, such as how cells change the organization of DNA to control gene expression.
Reference: Kai Sandvold Beckwith, Andreas Brunner, Natalia Rosalia Morero, Ralf Jungmann, Jan Ellenberg. Nanoscale DNA tracing reveals the self-organization mechanism of mitotic chromosomes. Cell, 2025. doi:10.1016/j.cell.2025.02.028
