How DNA is packaged for cell division




In the journal "Science", research groups from Heidelberg and Würzburg present the inner workings of the molecular machinery that forms DNA into chromosomes before cell division.

Human cells perform a technical feat when accommodating information in the smallest spaces. Each time a cell divides, it bundles the four-meter-long DNA into 46 tiny packets, each only a few millionths of a meter long.

Research groups at the European Molecular Biology Laboratory EMBL Heidelberg and Julius Maximilians University Würzburg (JMU) have discovered how a family of DNA motor proteins packages loosely arranged DNA strands into compact individual chromosomes during cell division.

Condensin forms loops of DNA

It was not until 2018 that Christian Häring and his team at EMBL Heidelberg showed that condensin molecules form DNA loops - providing a possible explanation for chromosome formation. However, the mechanism by which the protein complex accomplishes this feat remained unclear.

We have been working on this problem for a long time. But only now, by combining different experimental approaches, have we found an answer," says Häring. The former group leader at EMBL Heidelberg is currently a professor at the JMU Biozentrum. Here he heads the Department of Biochemistry and Cell Biology.

Observing individual molecules at work

The team had success with carefully designed experiments. They also observed and manipulated individual condensin molecules as they formed DNA loops. This revealed how different complex parts work together like a molecular machine: one part holds the DNA in place like an anchor, while the other acts as a motor, moving the DNA forward to create a long loop.

Like other motor proteins, condensin moves in "steps" along with the DNA, burning cellular energy in the form of ATP. However, these steps are 500 times longer than other DNA motor proteins, although the energy expenditure is about the same. "It's like a Formula 1 race car with the energy efficiency of an e-bike," says Indra Shaltiel. The JMU researcher is the first author of the study, which has now been published in the journal Science.

Other processes in the genome run similarly.

"Thanks to advances in cryo-electron microscopy, we could visualize this complex mechanism with unprecedented precision," says senior author Sebastian Eustermann, group leader at EMBL Heidelberg.

"We were able to see condensin in action and identify the molecular choreography by which ATP drives its motor activity - an important step towards understanding DNA loop formation. Similar loops and related molecular machinery have been detected in various genomic processes, including the control of gene on/off switching between cell divisions. Therefore, our findings may have even broader implications."

Condensins belong to one of the evolutionarily oldest families of chromosomal proteins. The discovery of this new mechanism opens up a whole new area of research.

"Members of the motor protein class, to which condensin belongs, are probably essential for all life on Earth," Häring said. "Obviously, we are just beginning to understand what role they play and how they might be affected in human cells."

Comments

Post a Comment

Popular posts from this blog

Monkeypox - the next exciting zoonosis

Image
There has been an unusual increase in monkeypox infections in Europe and the USA in recent weeks. The cause is not yet clear. What is monkeypox? Monkeypox is caused by the Orthopoxvirus simiae, a relative of the human pox viruses (variola, smallpox) and cowpox viruses. Monkeypox is a regular occurrence in Africa, probably transmitted from rodents to monkeys, sometimes to humans. They are pretty rare outside Africa. Smallpox (variola) was a dreaded infectious disease until the last century, which is hopefully a thing of the past thanks to consistent worldwide control and large-scale vaccination campaigns - in 1980, the WHO declared smallpox eradicated. Compulsory vaccination was abolished in the FRG in 1976 and in the GDR in 1982. This vaccination was carried out at an infant age; older people usually bear extensive scars on their upper arms. Smallpox also raged horribly in Europe before vaccination, which is why the reports of monkeypox are spreading so much fear right now. According t...
Read more

Miracle weapon headache tablets: How aspirin can help in everyday life

Image
It is one of the best-known medicines on the market and is freely available in almost every country: The headache tablet. The fact that it not only helps against a buzzing head after a party but is a real all-rounder among medicines is shown by its excellent side effects, which research from the natural sciences reveals. A milestone in the natural sciences is the invention of acetylsalicylic acid (ASA), marketed in 1899, initially under the name Aspirin. Today, this active ingredient is an essential component of many headache tablets. Its origin was discovered more than 2,000 years ago to reduce fever and relieve pain: the substance salicyl contained in willow bark. For example, the physician Hippocrates, born in 460 BC, used it. The acetylsalicylic acid contained in most headache tablets relieves pain and reduces fever. But Aspirin can do much more: here are a few hacks: Aspirin ASS not only helps against headaches. Not just for headaches: ASA A dissolved headache tablet in flower wat...
Read more