DNA molecules carry genetic instructions for our cells. Most of the time that DNA is tightly coiled around proteins. A new study shows that the coiled DNA acts much like the string on a yo-yo. And that’s good, because by being rolled up, each cell can store a lot of instructions.
If each piece of DNA from a human cell were laid end to end, the collection of strands would stretch about two meters (6.6 feet) long. Yet these long genetic molecules must fit into a cell nucleus just 10 micrometers (0.0004 inch) in diameter. How can the body shoehorn so much DNA in? It wraps each strand of DNA around a series of proteins called histones (HISS-toanz).
Eight histones clump together, and a section of DNA wraps roughly twice around the package, forming a nucleosome (NU-clee-oh-zoam). DNA loops into one nucleosome after another along its entire length — hundreds of thousands of nucleosomes in all. This gives DNA the appearance of a beaded necklace, explains Jaya Yodh. A biophysicist, she works at the University of Illinois at Urbana-Champaign. (A biophysicist studies the physical forces in biological systems.) Those beads pack together, cramming the entire DNA strand into a very tiny space.
Such cramped conditions are great for storing DNA. But for cells to use the genes on each DNA strand, the coils have to unwind. Yodh and her team wondered whether the flexibility of DNA played a role in that unwinding.
To find out, they used a single nucleosome. Its DNA was wound around a set of histones, kind of like the string on a yo-yo. Unlike a yo-yo, however, both ends of the nucleosome’s DNA hung free. (When inside a cell, those ends would connect to other nucleosomes.) At two points on the nucleosome, the researchers added fluorescent dye. This allowed them to track that part of the DNA as it unwrapped from the histones.
The researchers then attached a long DNA “tether” to one of the loose ends of the DNA strand. At the end of the tether, they added a 1-micrometer (0.00004-inch) plastic bead. The scientists attached the untethered end of the DNA to a microscope slide. That slide was coated with special “sticky” molecules that acted like glue. The team then anchored the plastic bead (and DNA tether) with a laser beam; energy from that beam kept the bead from moving.
At the beginning, the DNA was tightly wrapped around the histones. But when the researchers pulled back on the microscope slide, it tugged on the DNA. This caused it to unwind like the string on a yo-yo.
The strand unwound easily when the team pulled on stiff sections of DNA, Yodh notes. But when they came to a flexible section of the DNA, the strand stopped uncoiling. The team had to pull much harder to make that strand again continue to unroll.
“The flexible sections are better able to wrap around the histones,” Yodh explains, so they tend to stay put. That tends to make each nucleosome fairly stable.
Her team published its findings online March 12 in Cell.
How they did it
The scientists made the DNA strand, creating its stiff and flexible sections. Although this DNA was made in the laboratory, its structure was very similar to what occurs naturally, Yodh says. Indeed, she speculates that the way it responded is likely to mirror what occurs to the DNA in our cells.
Stiff sections of DNA could help guide the cell’s machinery, she suspects. This would help ensure that DNA is read in the proper direction. Her team is now studying DNA sequences — parts of a strand — to see if stiff sections match up to the places where genes indeed are read. If so, changes in DNA sequences — mutations — might alter a strand’s flexibility. And that might affect how its genes are read, and used, inside cells.
“As with all good science, this raises more questions than answers,” says Andrew Andrews, who did not take part in the new study. He’s a geneticist at Fox Chase Cancer Center in Philadelphia, Pa. To understand the role of physical forces in DNA wrapping and unwrapping, scientists will need to look closely at where nucleosomes are positioned, he says. But this study could have a big impact on nucleosome research, he says.
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biophysics The study of physical forces as they relate to biological systems. People who work in this field are known as biophysicists.
cell The smallest structural and functional unit of an organism. Typically too small to see with the naked eye,it consists of watery fluid surrounded by a membrane or wall. Animals are made of anywhere from thousands to trillions of cells, depending on their size.
chromosome A single threadlike piece of coiled DNA found in a cell’s nucleus. A chromosome is generally X-shaped in animals and plants. Some segments of DNA in a chromosome are genes. Other segments of DNA in a chromosome are landing pads for proteins. The function of other segments of DNA in chromosomes is still not fully understood by scientists.
DNA (short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.
fluorescent Capable of absorbing and reemitting light. That reemitted light is known as a fluorescence.
force Some outside influence that can change the motion of a body, hold bodies close to one another, or produce motion or stress in a stationary body.
gene (adj. genetic) A segment of DNA that codes, or holds instructions, for producing a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.
genetic Having to do with chromosomes, DNA and the genes contained within DNA. The field of science dealing with these biological instructions is known as genetics. People who work in this field are geneticists.
histone A type of protein found in the nucleus of cells. Strands of DNA coil around sets of eight of these proteins to fit inside of cells. Each chromosome within a cell has its own strand of DNA. So with 23 pairs of human chromosomes, every human cell should host 46 strands of DNA — each wrapped around hundreds of thousands of histones. This tight coiling helps the body to pack its long DNA molecules into very tiny spaces.
microscope An instrument used to view objects, like bacteria, or the single cells of plants or animals, that are too small to be visible to the unaided eye.
molecule An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).
mutation Some change that occurs to a gene in an organism’s DNA. Some mutations occur naturally. Others can be triggered by outside factors, such as pollution, radiation, medicines or something in the diet. A gene with this change is referred to as a mutant.
nucleosome A bead-like structure that forms as DNA wraps 1.7 times around a cluster of eight proteins, called histones, inside a cell’s nucleus. The hundreds of thousands of nucleosomes found on a single strand of DNA help to pack the DNA into a very small space.
nucleus Plural is nuclei. (in biology) A dense structure present in many cells. Typically a single rounded structure encased within a membrane, the nucleus contains the genetic information.
proteins Compounds made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. The hemoglobin in blood and the antibodies that attempt to fight infections are among the better known, stand-alone proteins.Medicines frequently work by latching onto proteins.
sequence (in genetics) A string of DNA bases, or nucleotides, that provide instructions for building molecules in a cell. They are represented by the letters A,C,T and G.
slide In microscopy, the piece of glass onto which something will be attached for viewing under the device’s magnifying lens.
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Original Journal Source: T.T.M. Ngo et al. Asymmetric unwrapping of nucleosomes under tension directed by DNA local flexibility. Cell. Published online March 12, 2015. doi: 10.1016/j.cell.2015.02.001.