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DNA protected during cell division thanks to elastic chromosomes

4 May 2022
A research team led by VU physicists Gijs Wuite, Erwin Peterman and Chase Broedersz has developed a new method of studying human chromosomes – and thus DNA – with optical tweezers.

The researchers discovered that chromosomes are highly elastic during cell division, preventing the DNA from getting damaged. The team also discovered that one specific protein, TOP2A, plays an important role in the structure of chromosomes. Published today in Nature, the study is the result of a collaboration with a team of biologists from the University of Copenhagen, led by Ian Hickson.

Much higher measurement precision
Professor in biophysics Gijs Wuite: “We are the first to use optical tweezers to measure the mechanical properties of chromosomes. Until now, mechanical measurements have been done with small needles, which has already provided a lot of information, but we have now developed instrumentation with a much higher measuring precision. In addition, we are combining our measurements with advanced fluorescence microscopy, which together opens up a whole new world of possibilities to closely examine human chromosomes.”

Researchers now have a better understanding of the problems that can occur during cell division: unravelling the secrets of ‘healthy’ cell division is crucial to understanding what can go wrong. Too many small errors during cell division can cause serious illness. This new method could be used, for example, to investigate congenital defects that lead to significant DNA damage during cell division, like Fragile X syndrome.

A few meters of DNA
The Nature article’s first author, Anna Meijering, obtained her doctorate with this study at VU Amsterdam in 2021. “Each human cell contains a few meters of DNA”, she explains. “That DNA must be copied during cell division and distributed to the daughter cells without getting tangled in the process. Not an easy feat! To accomplish this, the DNA forms an enormously compact structure: the chromosome. This structure is difficult to examine with microscopy or other established techniques, precisely because of how enormously compact the DNA is.”

Meijering and her colleagues thus developed a new method of pulling chromosomes – isolated from their cells – with optical tweezers. The researchers then measured how the chromosomes responded to this stretching. “It’s like pulling a string versus pulling a rubber band”, Meijering says. “By measuring how it reacts, you can learn more about its underlying structure. We found that different parts within the chromosome will take turns absorbing the largest amount of stretch, protecting the structure as a whole from major deformations.” Chase Broedersz adds: “The chromosome becomes extremely rigid when it is stretched: it becomes stiffer. With a regular rubber band, you have to pull twice as hard if you want to stretch it twice as much. The chromosome behaves differently: the harder you pull on it, the less it responds to the force by not stretching much further.”

ERC Advanced Grant
The research was done within the European research project Chromavision. Follow-up research is already underway in the MONOCHROME research project, which started last year. Professor Gijs Wuite was awarded an ERC Advanced Grant for MONOCHROME in 2020.

Photo: First author Anna Meijering is working on an experiment. Photographer: Anne Reitsma