Researchers 'unzip' molecules to measure interactions keeping DNA packed in cells

January 28, 2009
A DNA molecule containing a nucleosome is unzipped using a microsphere held in an optical trap, allowing precise mapping of histone-DNA interactions within the nucleosome. Yellow dots indicate the locations of strong interactions, determined to near-base pair accuracy.

(PhysOrg.com) -- Anyone who has ever battled a stuck zipper knows it's a good idea to see what's stuck, where and how badly -- and then to pull hard. A Cornell research team's experiments involve the "unzipping" of single DNA molecules. By mapping the hiccups, stoppages and forces along the way, they have gained new insight into how genes are packed and expressed within cells.

The research, "High-resolution dynamic mapping of histone-DNA interactions in a nucleosome," published online Jan. 11, 2009, in Nature Structural and Molecular Biology, was led by Michelle Wang, associate professor of physics and Howard Hughes Medical Institute Investigator. Collaborators on the project included physics graduate student Michael Hall and John Lis, the Barbara McClintock Professor of Molecular Biology and Genetics.

DNA - the molecules that contain genetic information - are nucleic acids often illustrated as long, thin strands of double helices. DNA fits inside cell nuclei by being wound like thread around proteins called histones, forming tightly packed bundles called nucleosomes. But that same DNA must often be uncoiled and accessed by such enzymes as RNA polymerase, which the researchers liken to a motor because it moves along the DNA in the process of gene transcription.

"There is this paradox," Lis explained. "On one hand you need compaction and the packing away of DNA. On the other hand, you need accessibility, so the cellular machines can read the information contained in the DNA."

Trying to understand what happens during that unwrapping process is at the heart of this research team's efforts. By unzipping each DNA double helix through a nucleosome using an optical trap -- a technique developed in Wang's lab -- they unwrapped strands of DNA from their histone cores, observing, with near-base pair accuracy, the interactions that took place along the way.

"Our hope is that if we can establish and understand the interactions within the nucleosome, we can begin to understand how the motor proteins can invade the nucleosome," Wang said.

Optical trapping involves a focused beam of light that can "trap" small objects. A refractive sphere is chemically attached to the DNA strand, and the optical trap moves the sphere, allowing the researchers to unzip the DNA strands apart by pulling, Hall explained. By doing so, the researchers re-created what happens in the cell when DNA uncoils from the histone core, and they measured the blips along the way -- for example, when the DNA strand had to be pulled apart from a protein molecule -- and how much force was needed to keep going.

"It's really like a zipper," Hall said. "And when there is a protein in there, it's kind of like you have a piece of cloth stuck. You know you can get it out, but you just have to pull harder, and then it pops out. That's basically the same way we can detect where the interactions are with the proteins."

The researchers have performed the first direct, precise measurements of histone-DNA interactions. Their findings could help uncover how changes to the histones or DNA sequences affect how motor proteins access genetic information in cells.

"If we have that knowledge, we can extrapolate that information to apply to different scenarios and different motor motions," Wang said.

Reference: Nature Structural and Molecular Biology, doi: 10.1038/nsmb.1526

Provided by Cornell University

Explore further: Ozone bubbles to eliminate wastewater micropollution

Related Stories

Ozone bubbles to eliminate wastewater micropollution

July 31, 2015

Ozone treatment efficiently removes many micropollutants contained in wastewater, but in some cases, it can lead to the formation of toxic byproducts. A new test informs on whether ozonation is a suitable technology for enhanced ...

New insights into the production of antibiotics by bacteria

July 31, 2015

Bacteria use antibiotics as a weapon and even produce more antibiotics if there are competing strains nearby. This is a fundamental insight that can help find new antibiotics. Leiden scientists Daniel Rozen and Gilles van ...

Cooking up altered states

July 31, 2015

Churning raw milk sufficiently creates butter. Squirting lemon juice coagulates it into curd. These two phenomena are not as straightforward as they sound on the molecular level.

Quantum matter stuck in unrest

July 31, 2015

Using ultracold atoms trapped in light crystals, scientists from the MPQ, LMU, and the Weizmann Institute observe a novel state of matter that never thermalizes.

It's alive, it's alive!

July 30, 2015

On June 3, 2015, more than a month before New Horizons, flying faster than speeding bullet, reached its rendezvous with the Pluto system, an astronomer at the Southwest Research Institute who is also a space artist posted ...

Recommended for you

New lizard named after Sir David Attenborough

August 3, 2015

A research team led by Dr Martin Whiting from the Department of Biological Sciences recently discovered a beautifully coloured new species of flat lizard, which they have named Platysaurus attenboroughi, after Sir David Attenborough.

'Snowball earth' might be slushy

August 3, 2015

Imagine a world without liquid water—just solid ice in all directions. It would certainly not be a place that most life forms would like to live.

A look at living cells down to individual molecules

August 3, 2015

EPFL scientists have been able to produce footage of the evolution of living cells at a nanoscale resolution by combining atomic force microscopy and an a super resolution optical imaging system that follows molecules that ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.