Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Proteins Transform DNA into "Molecular Velcro"

07.06.2004


Proteins critical for compacting DNA in preparation for cell division actually interact with the double helix to fashion it into a kind of “molecular Velcro,” researchers have discovered.


"When we began to pull it apart carefully, we saw it extend in a sawtooth pattern of force, like the click-click-click of Velcro unzipping," said HHMI investigator Carlos Bustamante.
Photo: Barbara Ries



The proteins, called condensins, are important for a variety of housekeeping processes in chromosomes, but the mechanics behind their function have been largely unknown. When the researchers alternately stretched and compressed a single molecule of DNA with condensins attached, they found that the DNA extended in stepwise “clicks,” akin to Velcro unzipping.

The successful manipulation of a single DNA molecule with condensin proteins attached makes it plausible to think about using a similar strategy to explore the machinery that processes chromosomes in the cell, said one of the study’s senior authors, Carlos Bustamante, a Howard Hughes Medical Institute researcher at the University of California, Berkeley.


Bustamante, Ryan B. Case, Nicholas R. Cozzarelli and their colleagues at Berkeley published their findings on June 3, 2004, in Science Express, which provides rapid electronic publication of selected articles from the journal Science.

“Until now, little was known about the function of condensins,” said Bustamante. “It was known that if the gene for the protein was knocked out, chromosomes failed to segregate properly in cell division. One daughter cell might receive all the DNA and the other none.”

Bustamante and his colleagues took note of earlier studies by another group of researchers that provided evidence that condensins appeared to induce “supercoiling” in DNA, which occurs when two helical molecules intertwine.

“We decided to try to develop a single-molecule assay, to see whether we could really understand the mechanism of this protein’s effects on DNA,” said Bustamante. “Even though there was no bulk assay for this protein’s activity, we thought that maybe we would get lucky and observe some activity at a single-molecule level.”

The researchers worked with a type of condensin found in the bacterium E. coli. Their experimental procedure consisted of attaching one end of a DNA molecule to a tiny plastic bead held by suction onto a micropipette. They then caused the DNA molecule to extend by flowing liquid past it, and exposed it to a solution containing the bacterial condensin protein. The researchers next added the energy-containing molecule ATP to the solution. After the ATP was added, they captured the other end of the condensin-treated DNA molecule with another plastic bead and proceeded to pull on the DNA with precisely measured force.

“We found that the DNA molecule had become much shorter in the presence of the condensin protein,” said Bustamante. “And when we began to pull it apart carefully, we saw it extend in a sawtooth pattern of force, like the click-click-click of Velcro unzipping.

“When we pulled again a second time, much to our surprise, the process reproduced identically every tooth in the sawtooth pattern. We had never seen anything like that. We really thought that we were only seeing noise in the stretching of the DNA, but instead we were seeing a perfect registry in the sawtooth pattern,” Bustamante said.

That perfect reproducibility strongly suggested to Bustamante and his colleagues that they were seeing a condensed structure with a well defined organization. “Every time we pulled it out and relaxed it, the molecule was able to return to the same initial or condensed form,” said Bustamante. In fact, the researchers pulled and relaxed the same DNA molecule dozens of times, seeing the same sawtooth pattern of extension and condensation each time.

They also found that the energy-containing ATP molecule appeared to play a regulatory role, rather than providing energy for the condensation reaction. When the researchers removed all excess ATP from the solution, they found that the condensin proteins continued to function. “That finding was a big surprise, because we expected the protein to be more like a motor that had to burn ATP every time it condensed,” said Bustamante. Also, when they removed the excess protein from the solution, the bound protein was able to recondense the DNA when the tension on the DNA was lowered.

The researchers’ analyses led them to propose a model of how the string of condensin proteins interacts to condense the DNA molecule. They theorize that the “heads” of the condensin proteins attach themselves sequentially and tightly to DNA. By attaching in this fashion, each protein “cooperates” with its neighbor, binding itself reversibly to the head of the next protein, thereby scrunching the DNA bit by bit into its condensed state. And when the researchers experimentally stretched the DNA molecule, the condensin heads popped apart sequentially, producing the sawtooth force extension pattern. But the heads remained bound to the DNA, so that when the force is lowered they can go back to their closed state and recondense the DNA molecule.

According to Bustamante, these studies of the bacterial condensin molecule will open the way to future studies of similar proteins that manipulate DNA and maintain chromosomal structure. “The actual mechanism by which these molecules actually carry out their function is unknown,” he said. “And so, we are very excited that we have been able to develop an assay that, for the first time, gives us an understanding of how these molecules may be acting at the molecular level.”

Jim Keeley | HHMI
Further information:
http://www.hhmi.org/news/bustamante3.html

More articles from Life Sciences:

nachricht Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland

nachricht Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>